Increase In Forearm Blood Flow Research Articles

Skin Wetting Attenuates the Thermal Strain of Older Adults Exposed to Very Hot and Dry Heat with Accompanying Activities of Daily Living

Heat waves cause more deaths and hospitalizations in the elderly relative to any other age group. Indoor cooling with an air conditioner is an effective strategy to prevent the deleterious health effects of heat. However, air conditioning may not be available to some due to limited access, rising energy costs, power outages, and/or industry/government-imposed rolling blackouts. Thus, there is a clear need to identify non-air conditioning dependent cooling strategies to attenuate excessive elevations in body temperature and associated physiological strain in the elderly during heat wave conditions. Purpose: We tested the hypothesis that supplemental skin wetting via water spray attenuates elevations in core temperature and the accompanying physiological strain in older adults exposed to very hot and dry heat with accompanying activities of daily living. Methods: In a randomized order, 10 older adults (4 Females/6 Males; 74 ± 5 years) were exposed to 3-hours of ambient heating, replicating peak environmental conditions during the 2018 Los Angeles heat wave (47 ºC, 15% relative humidity), with (water spray) or without (control) skin-wetting via tap temperature water (~40 g applied every 10-minutes). To simulate heat generation associated with activities of daily living, participants performed six 5-minute periods of light exercise (~3 METS; metabolic heat production: 2.93 ± 0.42 W/kg in control and 2.95 ± 0.44 W/kg in water spray) dispersed throughout the heat exposure. To maintain euhydration, participants consumed 3 mL/kg/hr of tap-temperature water. We assessed core and skin temperatures, heart rate, whole-body sweat rate, and forearm blood flow (as a surrogate of changes in skin blood flow). We compared data between control and water spray trials using one-tailed paired t-tests. Results: When compared to control, water spray reduced the increase in core temperature by 0.33 ± 0.43 °C (p=0.020), ending skin temperature by 1.83 ± 0.73 °C (p<0.001), and ending heart rate by 6 ± 9 bpm (p=0.033). Whole-body sweat rate was 2.12 ± 1.08 g/min lower with water spray compared to control (p<0.001). However, the increase in forearm blood flow was not different between control (154 ± 74 mL/min) and water spray (149 ± 93 mL/min) trials (p=0.400). Conclusion: These preliminary data show that supplemental skin-wetting via water spray attenuates the thermal (core and skin temperature) and associated physiological strain (heart rate and fluid-loss) of older adults exposed to extreme heat with accompanying activities of daily living. The downstream impact of this reduced thermal strain on cardiac and renal stress should be examined, as these are two of the main causes of heat-related morbidity and mortality. Supported by NIH R01AG069005 (CGC) and AHA 23POST1023065 (ZJM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Utilizing venous occlusion plethysmography to assess vascular effects: A study with buloxibutid, an angiotensin II type 2 receptor agonist.

Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open-label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra-arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 μg/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8-3.2 μg/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra-arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3-200 μg/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230-320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra-arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.

Forearm vascular conductance responses to rhythmic handgrip in young African American compared with Caucasian American women

Non-Hispanic African American (AA) individuals have a disproportionately high prevalence, and mortality rate of cardiovascular disease (CVD) compared to other populations. Previous studies have demonstrated that even young, healthy AA individuals have blunted flow-mediated dilation, attenuated vasodilatory responses to pharmacological infusions and rhythmic handgrip exercise (RHG), as well as higher arterial stiffness and exaggerated peripheral vasoconstriction to isometric handgrip exercise and other non-exercise-stimuli compared to Caucasian-American (CA) individuals. These studies indicate that vascular alterations occur early on in life of AA individuals, potentially contributing to elevated risk of CVD in this racial group. However, these racial disparities in vascular function have almost exclusively been studied in men. Herein, we tested the hypothesis that, similar to young AA men, young AA women will exhibit an attenuated increase in forearm blood flow (FBF) and forearm vascular conductance (FVC) during rhythmic handgrip exercise (RHG) compared to age-matched CA women. Forearm blood flow (FBF; duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured in young CA (n = 5) and AA (n = 5) women during rhythmic handgrip exercise performed at three workloads (15%, 30%, and 45% of maximal voluntary contraction (MVC)). FVC was calculated as FBF/MAP. Baseline FBF (CA: 66.0 ± 12.8 and AA: 61.6 ± 12.2 ml/min; mean ± SD, p = 0.30); FVC (CA: 0.8 ± 0.2 and AA: 0.7 ± 0.2 ml/min/mmHg; p = 0.16), MAP (CA: 82 ± 11 and AA: 88 ± 4 mmHg; p = 0.28), and MVCs (CA: 50 ± 4 and AA: 52 ± 5 kg; p = 0.35) were similar between the groups. Both groups exhibited intensity-dependent increases in FBF and FVC; however, contrary to our hypothesis, there were no race difference (mixed-model two-way ANOVA; FVC: race effect p = 0.18, intensity effect p < 0.0001, interaction p = 0.48). For instance, in response to RHG at 45%, CA had 384 ± 112% increase in FBF from baseline and AA had 499 ± 153% increase. Increase in FVC from baseline was 198 ± 76% for CA women and 314 ± 151% for AA women. MAP did not differ between the groups (e.g., ΔMAP at 45%; CA: 13 ± 11 vs AA: 9 ± 5, p = 0.41). These preliminary data suggest that the hyperemic response to rhythmic handgrip exercise in young African American women are similar to age-matched Caucasian-American women. Supported byKinesiology and Health Education UT Austin Start-up Account 19-2635-91. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Rapid onset vasodilation in response to forearm muscle contraction in Hispanic American and Caucasian American Adults

Hispanic Americans (HA) are the fastest growing ethnic populations in the U.S., estimated to double in the next four decades. According to NHANES 2013-2016 data, prevalence of type 2 diabetes (T2D) is 15.1% in HA men and 14.1% in HA women, compared to 9.4 and 7.3% in non-Hispanic Caucasian American (CA) men and women, respectively. Even HA children have a 5-fold higher rate of T2D compared to their age-matched CA counterparts. Impaired vascular function is a hallmark of T2D however, limited number of studies have investigated the effect of ethnicity on vascular function at rest and during exercise. To our knowledge, only one study has reported a higher flow-mediated dilation at rest in healthy HA compared to CA adults. Hence, the purpose of this study was to investigate the rapid onset vasodilation in response to a single muscle contraction of the forearm at progressively increasing intensity (20, 40, and 60% of maximum voluntary contraction (MVC)) in young, healthy HA compared to age- and weight-matched CA individuals. A single muscle contraction model was chosen to isolate the robust local vasodilatory responsiveness of the vasculature without increases in sympathetic nerve activity or large hemodynamic changes. We hypothesized that HA would demonstrate an attenuated forearm vascular conductance (FVC) and forearm blood flow (FBF) in response to skeletal muscle contractions, compared to CA group. Young, healthy HA (n=4) and CA (n=4) adults performed skeletal muscle contractions at 20%, 40 % and 60% of their maximum voluntary contraction (MVC). To isolate the effect of mechanical compression during muscle contractions, FBF and FVC responses to a brachial cuff inflation were also measured. Heart rate (ECG), mean arterial pressure (MAP; finger photoplethysmography) and forearm blood flow (FBF; duplex Doppler ultrasound) were measured. FVC was calculated as FBF/MAP. Baseline FBF (CA: 115.21 ± 48.9 and HA: 68.89 ± 21.9 ml/min; p=0.27), MAP (CA: 82 ± 7.48 and HA: 81 ± 2.87 mmHg; p=0.77), FVC (p=0.15), and MVCs (CA: 67 ± 26.8 and HA: 70 ± 7.4 kg; p=0.82) were similar between the groups. Following single muscle contractions, both groups exhibited an intensity dependent increase in FVC and FBF, however, there was no difference between HA and CA groups. For instance, following muscle contraction at 40% MVC, peak FVC (%Δ) was 251% ± 46.35 in HA and 189% ± 34.98 in CA (race effect p = 0.23, time effect = 0.01, interaction p = 0.029). Similarly, peak %Δ FBF or %Δ FVC following 60% contractions were similar between the groups (FVC: 327% ± 84.36 in HA vs. 286% ± 74.45 in CA (race effect p=0.62, time effect p<0.01, interaction effect p=0.01)). Both groups exhibited a similar response to brachial cuff inflation for peak FVC (p=0.21) and peak FBF (p=0.30). Our preliminary findings indicate that HA have a preserved rapid onset vasodilation in response to a single forearm contraction when compared to CA adults. Supported by Kinesiology and Health Education UT Austin Start-up Account 19-2635-91 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

GLOBAL REACH 2018: intra-arterial vitamin C improves endothelial-dependent vasodilatory function in humans at high altitude.

High altitude-induced hypoxaemia is often associated with peripheral vascular dysfunction. However, the basic mechanism(s) underlying high-altitude vascular impairments remains unclear. This study tested the hypothesis that oxidative stress contributes to the impairments in endothelial function during early acclimatization to high altitude. Ten young healthy lowlanders were tested at sea level (344m) and following 4-6 days at high altitude (4300m). Vascular endothelial function was determined using the isolated perfused forearm technique with forearm blood flow (FBF) measured by strain-gauge venous occlusion plethysmography. FBF was quantified in response to acetylcholine (ACh), sodium nitroprusside (SNP) and a co-infusion of ACh with the antioxidant vitamin C (ACh+VitC). The total FBF response to ACh (area under the curve) was ∼30% lower at high altitude than at sea level (P = 0.048). There was no difference in the response to SNP at high altitude (P = 0.860). At sea level, the co-infusion of ACh+VitC had no influence on the FBF dose response (P = 0.268); however, at high altitude ACh+VitC resulted in an average increase in the FBF dose response by ∼20% (P = 0.019). At high altitude, the decreased FBF response to ACh, and the increase in FBF in response to ACh+VitC, were associated with the magnitude of arterial hypoxaemia (R2 = 0.60, P = 0.008 and R2 = 0.63, P = 0.006, respectively). Collectively, these data support the hypothesis that impairments in vascular endothelial function at high altitude are in part attributable to oxidative stress, a consequence of the magnitude of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourns, with important implications for understanding the aetiology of high altitude-related vascular dysfunction. KEY POINTS: Vascular dysfunction has been demonstrated in lowlanders at high altitude (>4000m). However, the extent of impairment and the delineation of contributing mechanisms have remained unclear. Using the gold-standard isolated perfused forearm model, we determined the extent of vasodilatory dysfunction and oxidative stress as a contributing mechanism in healthy lowlanders before and 4-6 days after rapid ascent to 4300m. The total forearm blood flow response to acetylcholine at high altitude was decreased by ∼30%. Co-infusion of acetylcholine with the antioxidant vitamin C partially restored the total forearm blood flow by ∼20%. The magnitude of forearm blood flow reduction, as well as the impact of oxidative stress, was positively associated with the individual severity of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourns, with important implications for understanding the aetiology of high altitude-related changes in endothelial-mediated vasodilatory function.

Effects of 1 MHz Therapeutic Ultrasound on Limb Blood Flow and Microvascular Reactivity: A Randomized Pilot Trial.

A randomized, double-blind, placebo-controlled, cross-over study where continuous therapeutic ultrasound (CUS; at 0.4 W/cm2), pulsed therapeutic ultrasound (PUS; at 20% duty cycle, 0.08 W/cm2), both at 1 MHz, and placebo (equipment on, no energy provided) were randomized and applied over the forearm of the non-dominant arm for 5 min in 10 young, healthy individuals. Absolute and peak forearm blood flow (FBF) were measured via Venous Occlusion Plethysmography. FBF was measured before, halfway, and after (immediately and 5 min after) the therapeutic ultrasound (TUS) intervention. Post-ischemic peak FBF was measured 10 min before and 10 min after the TUS intervention. A two-way repeated measures ANOVA (group × time) was selected to assess differences in FBF before, during, and after TUS treatment, and for peak FBF before and after TUS treatment. FBF increased 5 min after TUS in CUS compared to placebo (2.96 ± 1.04 vs. 2.09 ± 0.63 mL/min/100 mL of tissue, p < 0.05). PUS resulted in the greatest increase in Peak FBF at 10 min after US (Δ = 3.96 ± 2.02 mL/min/100 mL of tissue, p = 0.06). CUS at 1 MHz was an effective treatment modality for increasing FBF up to 5 min after intervention, but PUS resulted in the greatest increase in peak FBF at 10 min after intervention.

Blunted hyperemic response to mental stress in young, non-Hispanic black men is not impacted by acute dietary nitrate supplementation.

Non-Hispanic black individuals suffer from an elevated prevalence of hypertension and cardiovascular disease (CVD) relative to other populations. This elevated disease risk is, in large part, related to impaired vascular function, secondary to reduced nitric oxide (NO) bioavailability. Emerging evidence suggests that dietary nitrate supplementation improves several cardiovascular parameters, including vascular function, in part by increased NO bioavailability. However, whether these findings extend to a population of black individuals is unknown. This study tested the hypothesis that forearm blood flow responses in young, non-Hispanic, black (BL) men during a mental stress challenge would be blunted relative to young, non-Hispanic, white (WH) men. We further hypothesized that acute dietary nitrate supplementation would improve this response in BL men. This study comprised two parts (phase 1 and phase 2). Phase 1 investigated the difference in blood flow responses between young, BL, and WH men. In contrast, phase 2 investigated the effect of acute nitrate supplementation on the responses in a subset of the BL men from phase 1. Eleven (nine for phase 2) BL and eight WH men (23 ± 3 vs. 24 ± 4 yr, respectively) participated in this double-blind, placebo-controlled, randomized, crossover study. During each visit, hemodynamic responses during 3 min of mental stress were assessed in the brachial artery using duplex Doppler ultrasound. Phase 1 was completed in one visit, whereas phase 2 was completed over two visits separated by ∼1 wk. During phase 2, data were collected before and 2-h postconsumption of a beverage either high in nitrate content or nitrate depleted. In phase 1, peak forearm blood flow (FBF; P < 0.001), total FBF (P < 0.01), and forearm vascular conductance (FVC; P < 0.001) were blunted in the BL. During phase 2, prebeverage responses were similar to phase 1 and were unaffected following beverage consumption (P > 0.05 vs. prebeverage for all variables). These data indicate that young, BL men have blunted microvascular vasodilatory responses to acute mental stress, which may not be altered following acute nitrate supplementation.NEW & NOTEWORTHY This study tested the hypothesis that non-Hispanic black (BL) men have a blunted forearm hyperemic response to mental stress, which would be augmented following acute nitrate supplementation. The increase in forearm blood flow during mental stress was attenuated in BL men and was not impacted by nitrate supplementation. This supports findings of altered vascular function in this population. This is especially important as BL experience a higher prevalence of stress, which contributes to CVD risk.

Functional sympatholysis is preserved in healthy young Black men during rhythmic handgrip exercise.

Black men have attenuated increases in forearm vascular conductance (FVC) and forearm blood flow (FBF) during moderate- and high-intensity rhythmic handgrip exercise compared with White men, but the underlying mechanisms are unclear. Here, we tested for the first time the hypothesis that functional sympatholysis (i.e., attenuation of sympathetic vasoconstriction in the exercising muscles) is impaired in Black men compared with White men. Thirteen White and 14 Black healthy young men were studied. FBF (duplex Doppler ultrasound) and mean arterial pressure (MAP; Finometer) were measured at rest and during rhythmic handgrip exercise at 30% maximal voluntary contraction. FVC was calculated as FBF/MAP. Sympathetic activation was induced via lower body negative pressure (LBNP) at -20 Torr for 2 min at rest and from the 3rd to the 5th min of handgrip. Sympathetic vasoconstriction was assessed as percent reductions in FVC during LBNP. The groups presented similar resting FVC, FBF, and MAP. During LBNP at rest, reductions in FVC were not different between White (-35 ± 10%) and Black men (-32 ± 14%, P = 0.616), indicating similar reflex-induced sympathetic vasoconstriction. During handgrip exercise, there were minimal reductions in FVC with LBNP in either group (White: -1 ± 7%; Black: +1 ± 8%; P = 0.523), indicating functional sympatholysis in both groups. Thus, contrary to our hypothesis, our findings indicate a preserved functional sympatholysis in healthy young Black men compared with White men, suggesting that this mechanism does not appear to contribute to reduced exercise hyperemia during moderate-intensity rhythmic handgrip in this population.

Cardiac baroreflex function and vascular reactivity recovery after aerobic exercise in patients with early cirrhosis.

To investigate the effects of aerobic exercise on the cardiac baroreflex function and vascular reactivity in patients with cirrhosis. Thirteen patients with cirrhosis were submitted to exercise and control intervention. At baseline and at 30 and 60 min following intervention, we evaluated cardiac baroreflex sensitivity (cBRS) and the baroreflex effectiveness index (BEI) using sequence technique. Vascular reactivity was assessed inducing reactive hyperemia before and 60 min after intervention. At baseline, there was no difference (P interaction = 0.848) between exercise (from 3.0 ± 0.34 to 14.60 ± 1.06 ml/100ml/min) and control sessions (from 2.38 ± 0.10 to 13.73 ± 1.05 ml/100ml/min) regarding the increase in forearm blood flow during reactive hyperemia. However, this response was higher postexercise (from 3.38 ± 0.31 to 16.58 ± 1.58 ml/100ml/min) than postcontrol intervention (from 2.04 ± 0.23 to 11.98 ± 1.16 ml/100ml/min, P interaction < 0.001). BEI increased at 30- and 60-min postexercise (from 32 ± 7 to 42 ± 7 and 46 ± 7%), but not after control intervention (from 33 ± 6 to 31 ± 5 and 33 ± 7%, P interaction = 0.014). In contrast, cBRS decreased at 30-min postexercise (from 10.3 ± 1.9 to 8.2 ± 1.4 and 10.3 ± 2.1 ms/mmHg) and increased postcontrol intervention (from 7.9 ± 0.9 to 10.5 ± 1.5 and 10.3 ± 1.3 ms/mmHg, P interaction = 0.012). The results suggest that a single bout of aerobic exercise improved cardiac baroreflex function and increased vascular reactivity in patients with early-stage cirrhosis.

Acute Soy Supplementation Improves 20-km Time Trial Performance, Power, and Speed.

Isoflavones, a chemical class of phytoestrogens found in soybeans and soy products, may have biological functions similar to estradiol. After binding with ERβ or perhaps independently of estrogen receptors, isoflavones may augment vascular endothelial relaxation, contributing to improved limb blood flow. To determine if acute fermented soy extract supplementation influences 20-km time trial cycling performance and cardiac hemodynamics compared with a placebo. Subjects included 25 cyclists and triathletes (31 ± 8 yr, V˙O2peak: 55.1 ± 8.4 mL·kg·min). Each subject completed a V˙O2peak assessment, familiarization, and two 20-km time trials in randomized order after ingestion of a fermented soy extract supplement or placebo. The fermented soy extract consisted of 30 g powdered supplement in 16 fl. ounces of water. The placebo contained the same quantities of organic cocoa powder and water. Each trial consisted of 60 min of rest, 30 min at 55% Wpeak, and a self-paced 20-km time trial. Soy supplementation elicited a faster time to 20-km completion (-0.22 ± 0.51 min; -13 s), lower average HR (-5 ± 7 bpm), and significantly greater power (7 ± 3 W) and speed (0.42 ± 0.16 km·h) during the last 5 km of the time trial compared with placebo. Analysis of the results by relative fitness level (<57 vs ≥ 57 mL⋅kg⋅min) indicated that those with a higher level of fitness reaped the largest performance improvement alongside a reduced HR (-5 ± 7 bpm). Ingestion of a fermented soy extract supplement improved sprint-distance performance through improvements in both power and speed. For those with great aerobic fitness, soy supplementation may help to decrease cardiac demand alongside performance improvement.

Role of Mitochondrial Aldehyde Dehydrogenase in Nitroglycerin-Mediated Vasodilation: Observations Concerning the Dose-Response Relationship.

The mechanism of the bioactivation of nitroglycerin has long been controversial, with a number of suggested enzymatic pathways. More recently, aldehyde dehydrogenase-2 (ALDH-2) has been reported as the important enzyme involved in the bioactivation of nitroglycerin at therapeutically relevant concentrations. Other previously described enzyme systems can also bioactivate nitroglycerin, but only at concentrations, which are significantly higher than achieved in clinical practice. This study investigated the vascular response to nitroglycerin given over a wide range of concentrations in subjects with and without the ALDH-2 Glu504Lys polymorphism, a common genetic variant that greatly reduces the activity of ALDH-2 (n = 10 in both groups). Forearm blood flow (FBF) responses to a brachial artery infusion of nitroglycerin were assessed using venous occlusion plethysmography. Intra-arterial infusion of nitroglycerin caused a significant increase in FBF beginning at 0.464 µg/min with increasing responses seen in both groups at all infusion rates. However, there were no differences in the FBF responses to nitroglycerin in those with and without the ALDH-2 polymorphism, suggesting that ALDH-2 is not solely responsible for the bioactivation of nitroglycerin at either low (therapeutically relevant) or high concentrations of nitroglycerin.

Attenuated Skeletal Muscle Contraction‐Induced Rapid Onset Vasodilation in African Americans

A number of studies have demonstrated that African Americans (AA) have a blunted ability to vasodilate at rest compared to Caucasian Americans (CA). Recently, our laboratory has demonstrated that AA have an attenuated forearm vascular conductance (FVC) response to rhythmic handgrip exercise at moderate and high intensities. Whether these differences in vasodilation also occur at the immediate onset of exercise remains unknown. Herein, we tested the hypothesis that AA subjects have an attenuated increase in FVC following a single muscle contraction, compared to CA subjects. A single muscle contraction model was chosen since it allows for isolation of rapid and robust local vasodilatory responses that are independent of large changes in systemic hemodynamics or sympathetic activation. Young, healthy AA (n = 4) and CA (n = 4) men performed single forearm contractions at 20%, 40%, and 60% of their maximum voluntary contraction (MVC). Heart rate (ECG), arterial blood pressure (Finometer), and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured. FVC was calculated as forearm blood flow (FBF)/mean arterial pressure (MAP). Baseline FVC (CA: 1.04 ± 0.18 and AA: 1.31 ± 0.11 ml/min/mmHg; p = 0.26), FBF (CA: 99.5 ± 16.1 and AA: 105.9 ± 8.7 ml/min; p = 0.54), MAP (CA: 82 ± 2 and AA: 84 ± 2 mmHg; p = 0.46) and MVCs (CA: 56 ± 1 and AA: 58 ± 3 kg; p = 0.45) were similar between the groups. Following single forearm contraction, both groups exhibited intensity‐dependent increases in FBF and FVC; however, these responses were significantly attenuated in AA at all intensities compared to CA. For instance, in response to 20% MVC single contractions, AA had a 34 ± 10% increase in FVC from baseline compared to a 86 ± 31% increase in CA (mixed‐model ANOVA; p &lt; 0.001), and in response to 60% MVC single contractions, AA had a 132 ± 9% increase in FVC from baseline compared to a 198 ± 30% in CA (mixed‐model ANOVA; p &lt; 0.001). These preliminary data suggest that AA have blunted vasodilation in response to single forearm contractions at mild, moderate and high‐intensity workloads.Support or Funding InformationSupported by UTA College of Nursing and Healthy InnovationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Acute Effect of Aerobic Exercise on Cardiovascular Reactivity of Overweight Males

Overweight compared to normal weight individuals typically possess reduced limb blood flow at rest and during mental challenge. The effect of a single bout of aerobic exercise on cardiovascular reactivity of young overweight males, however, is undetermined. Thus, the purpose was to examine the cardiovascular reactivity response of overweight males to mental challenge before and after acute aerobic exercise. Fifteen normal weight (NW) males with body mass index (BMI) between 18 and 25 kg/m2 and 15 overweight males (OW) with BMI > 25 kg/m2 aged 18-30 years acted as participants. All males underwent a 5-min Stroop task before and after one single 30-min bout of cycle exercise at 65% of maximal oxygen uptake (VO2max). Heart rate, blood pressure, arterial stiffness, and forearm blood flow (FBF) were assessed during Stroop task before and after acute exercise. Arterial stiffness of the OW was significantly higher than NW during Stroop before (p =0.01) and after exercise (p = 0.001). After exercise, the OW had significantly smaller increase in FBF throughout Stroop (p = 0.04) compared to NW. The smaller increase in FBF throughout the Stroop in the OW was also accompanied by higher Stroop errors compared to that of NW (p = 0.01). Stroop errors were positively correlated with BMI, waist circumference, waist/hip ratio, and body fat percentage, whereas post-exercise FBF was positively correlated with VO2max (p < 0.05). Being overweight was associated with a blunted FBF reactivity response and a greater number of errors during the Stroop task.

Is endothelial microvascular function equally impaired among patients with chronic Chagas and ischemic cardiomyopathy?

BackgroundChronic Chagas cardiomyopathy (CCC) and cardiomyopathies due to other etiologies involve differences in pathophysiological pathways that are still unclear. Systemic microvascular abnormalities are associated with the pathogenesis of ischemic heart disease. However, systemic microvascular endothelial function in CCC remains to be elucidated. Thus, we compared the microvascular endothelial function of patients presenting with CCC to those with ischemic cardiomyopathy disease. MethodsMicrovascular reactivity was assessed in 21 patients with cardiomyopathy secondary to Chagas disease, 21 patients with cardiomyopathy secondary to ischemic disease and 21 healthy controls. Microvascular blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh). ResultsPeak increase in forearm blood flow with ACh iontophoresis in relation to baseline was greater in healthy controls than in patients with heart disease (controls: 162.7 ± 58.4% vs. ischemic heart disease: 74.1 ± 48.3% and Chagas: 85.1 ± 68.1%; p < 0.0001). Patients with Chagas and ischemic cardiomyopathy presented similar ACh-induced changes from baseline in skin blood flow (p = 0.55). ConclusionEndothelial microvascular function was equally impaired among patients with CCC and ischemic cardiomyopathy.

Inhibition of Na+/K+‐ATPase and KIR channels abolishes hypoxic hyperaemia in resting but not contracting skeletal muscle of humans

Increasing blood flow (hyperaemia) to exercising muscle helps match oxygen delivery and metabolic demand. During exercise in hypoxia, there is a compensatory increase in muscle hyperaemia that maintains oxygen delivery and tissue oxygen consumption. Nitric oxide (NO) and prostaglandins (PGs) contribute to around half of the augmented hyperaemia during hypoxic exercise, although the contributors to the remaining response are unknown. In the present study, inhibiting NO, PGs, Na+ /K+ -ATPase and inwardly rectifying potassium (KIR ) channels did not blunt augmented hyperaemia during hypoxic exercise beyond previous observations with NO/PG block alone. Furthermore, although inhibition of only Na+ /K+ -ATPase and KIR channels abolished hyperaemia during hypoxia at rest, it had no effect on augmented hyperaemia during hypoxic exercise. This is the first study in humans to demonstrate that Na+ /K+ -ATPase and KIR channel activation is required for augmented muscle hyperaemia during hypoxia at rest but not during hypoxic exercise, thus providing new insight into vascular control. Exercise hyperaemia in hypoxia is augmented relative to the same exercise intensity in normoxia. During moderate-intensity handgrip exercise, endothelium-derived nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute to ∼50% of the augmented forearm blood flow (FBF) response to hypoxic exercise (HypEx), although the mechanism(s) underlying the remaining response are unclear. We hypothesized that combined inhibition of NO, PGs, Na+ /K+ -ATPase and inwardly rectifying potassium (KIR ) channels would abolish the augmented hyperaemic response in HypEx. In healthy young adults, FBF responses were measured (Doppler ultrasound) and forearm vascular conductance was calculated during 5min of rhythmic handgrip exercise at 20% maximum voluntary contraction under regional sympathoadrenal inhibition in normoxia and isocapnic HypEx (O2 saturation ∼80%). Compared to control, combined inhibition of NO, PGs, Na+ /K+ -ATPase and KIR channels (l-NMMA+ketorolac+ouabain+BaCl2; Protocol 1; n=10) blunted the compensatory increase in FBF during HypEx by ∼50% (29±6mLmin-1 vs. 62±8mLmin-1 , respectively, P<0.05). By contrast, ouabain+BaCl2 alone (Protocol 2; n=10) did not affect this augmented hyperaemic response (50±11mLmin-1 vs. 60±13mLmin-1 , respectively, P>0.05). However, the blocked condition in both protocols abolished the hyperaemic response to hypoxia at rest (P<0.05). We conclude that activation of Na+ /K+ -ATPase and KIR channels is involved in the hyperaemic response to hypoxia at rest, although it does not contribute to the augmented exercise hyperaemia during hypoxia in humans.

Evaluation of endothelial function by VOP and inflammatory biomarkers in patients with arterial hypertension.

Hypertension is associated with microcirculatory impairment. Our objectives were to evaluate endothelial function and inflammatory biomarkers in patients with resistant (RH) and mild to moderate (MMH) arterial hypertension in comparison to normotensives (control group-CG). Three groups, 25 patients each, have been investigated, by anamnesis, venous occlusion plethysmography (VOP) and serum determination of adhesion molecules (VCAM, ICAM), adiponectin, endothelin and C-reactive protein (CRP). Patients not using statins and with or without blood pressure control were also analyzed. RH group showed smaller percentage increase of maximum forearm blood flow (FBF) (endothelial-dependent vasodilatation) than controls (p < 0.05), but no significant difference could be detected between MMH and CG groups on maximum FBF and minimum vascular resistance post-ischemia. RH and MMH groups showed higher resistance averages compared to controls (p < 0.05). Uncontrolled BP in hypertensive patients showed worse results for blood flow and resistance. Endothelial-independent vasodilatation was not affected. Endothelin levels were higher in RH and MMH groups (p < 0.05) not using statins. CRP was significantly higher only in RH compared to CG (p < 0.05). In conclusion patients with severe hypertension and lack of blood pressure control showed greater impairment of endothelial function with higher CRP and endothelin levels.

ВЗАИМОСВЯЗЬ ПОЛИМОРФИЗМА ГЕНОВ ЭНДОТЕЛИАЛЬНОЙ NO-СИНТАЗЫ (G894T, T786C) И ГЕНА ЭНДОТЕЛИНА-1 (G5665T) С ЭФФЕКТИВНОСТЬЮ ТЕРАПИИ У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ ПОСЛЕ ПЕРЕНЕСЕННОГО ИШЕМИЧЕСКОГО ИНФАРКТА ГОЛОВНОГО МОЗГА

Background. Gene polymorphism of the endothelial NO-synthase (e-NOS) (G894T, T786C) and endothelin-1 (EDN-1) (G5665T) may be associated with a different response of patients with arterial hypertension (AH) to endotheliotropic therapy (ET).The aim of the study was to investigate the interrelation of the gene polymorphism of the e-NOS (G894T, T786C) and EDN-1 (G5665T) with the efficacy of therapy in patients with arterial hypertension after previous ischemic stroke.Material and methods: 65 people with arterial hypertension of II degree after previous ischemic stroke were examined. In all the patients, genotypes of e-NOS genes (G894T, T786C) and EDN-1 (G5665T) gene were determined.Endothelial function and vascular wall stiffness parameters were assessed in subgroups of homozygotes for dominant alleles (SGA) and in subgroups containing a recessive allele (SGB) before and after 12 weeks of ET.Results: Patients of SGB of e-NOS (G894T, T786C) and EDN-1 (G5665T) genes did not show a significant increase in forearm blood flow (FBF) and the percentage of target values of this parameter was lower compared to that in SGA.There was no significant decrease in the pulse wave velocity (PWV) in patients of EDN-1 (G5665T) gene SGB. The percentage of achievement of the target values of PWV in SGB was lower compared to that in SGA.Conclusions: Gene polymorphism of the e-NOS (G894T, T786C) and EDN-1 (G5665T) is not associated with the hypotensive effect of the drugs. The effect of the G894T e-NOS gene, T786C e-NOS gene and the G5665T EDN-1 gene correlated with the efficacy of endothelial dysfunction correction, which is manifested by the absence of a significant increase in FBF in carriers of genotypes with recessive alleles. The interrelation of the G5665T EDN-1 gene with the efficiency of correction of increased pulse wave velocity has been revealed, which is manifested by the absence of a significant lowering of this parameter in carriers of genotype with recessive alleles.

Fire Simulation and Cardiovascular Health in Firefighters.

Background:Rates of myocardial infarction in firefighters are increased during fire suppression duties, and are likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assessed the effects of simulated fire suppression on measures of cardiovascular health in healthy firefighters.Methods:In an open-label randomized crossover study, 19 healthy firefighters (age, 41±7 years; 16 males) performed a standardized training exercise in a fire simulation facility or light duties for 20 minutes. After each exposure, ex vivo thrombus formation, fibrinolysis, platelet activation, and forearm blood flow in response to intra-arterial infusions of endothelial-dependent and -independent vasodilators were measured.Results:After fire simulation training, core temperature increased (1.0±0.1°C) and weight reduced (0.46±0.14 kg, P<0.001 for both). In comparison with control, exposure to fire simulation increased thrombus formation under low-shear (73±14%) and high-shear (66±14%) conditions (P<0.001 for both) and increased platelet-monocyte binding (7±10%, P=0.03). There was a dose-dependent increase in forearm blood flow with all vasodilators (P<0.001), which was attenuated by fire simulation in response to acetylcholine (P=0.01) and sodium nitroprusside (P=0.004). This was associated with a rise in fibrinolytic capacity, asymptomatic myocardial ischemia, and an increase in plasma cardiac troponin I concentrations (1.4 [0.8–2.5] versus 3.0 [1.7–6.4] ng/L, P=0.010).Conclusions:Exposure to extreme heat and physical exertion during fire suppression activates platelets, increases thrombus formation, impairs vascular function, and promotes myocardial ischemia and injury in healthy firefighters. Our findings provide pathogenic mechanisms to explain the association between fire suppression activity and acute myocardial infarction in firefighters.Clinical Trial Registration:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01812317.

Pyr1]Apelin-13(1-12) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr1]Apelin-13.

Aims: Apelin is a predicted substrate for ACE2, a novel therapeutic target. Our aim was to demonstrate the endogenous presence of the putative ACE2 product [Pyr1]apelin-13(1–12) in human cardiovascular tissues and to confirm it retains significant biological activity for the apelin receptor in vitro and in vivo. The minimum active apelin fragment was also investigated.Methods and Results: [Pyr1]apelin-13 incubated with recombinant human ACE2 resulted in de novo generation of [Pyr1]apelin-13(1–12) identified by mass spectrometry. Endogenous [Pyr1]apelin-13(1–12) was detected by immunostaining in human heart and lung localized to the endothelium. Expression was undetectable in lung from patients with pulmonary arterial hypertension. In human heart [Pyr1]apelin-13(1–12) (pKi = 8.04 ± 0.06) and apelin-13(F13A) (pKi = 8.07 ± 0.24) competed with [125I]apelin-13 binding with nanomolar affinity, 4-fold lower than for [Pyr1]apelin-13 (pKi = 8.83 ± 0.06) whereas apelin-17 exhibited highest affinity (pKi = 9.63 ± 0.17). The rank order of potency of peptides to inhibit forskolin-stimulated cAMP was apelin-17 (pD2 = 10.31 ± 0.28) > [Pyr1]apelin-13 (pD2 = 9.67 ± 0.04) ≥ apelin-13(F13A) (pD2 = 9.54 ± 0.05) > [Pyr1]apelin-13(1–12) (pD2 = 9.30 ± 0.06). The truncated peptide apelin-13(R10M) retained nanomolar potency (pD2 = 8.70 ± 0.04) but shorter fragments exhibited low micromolar potency. In a β-arrestin recruitment assay the rank order of potency was apelin-17 (pD2 = 10.26 ± 0.09) >> [Pyr1]apelin-13 (pD2 = 8.43 ± 0.08) > apelin-13(R10M) (pD2 = 8.26 ± 0.17) > apelin-13(F13A) (pD2 = 7.98 ± 0.04) ≥ [Pyr1]apelin-13(1–12) (pD2 = 7.84 ± 0.06) >> shorter fragments (pD2 < 6). [Pyr1]apelin-13(1–12) and apelin-13(F13A) contracted human saphenous vein with similar sub-nanomolar potencies and [Pyr1]apelin-13(1–12) was a potent inotrope in paced mouse right ventricle and human atria. [Pyr1]apelin-13(1–12) elicited a dose-dependent decrease in blood pressure in anesthetized rat and dose-dependent increase in forearm blood flow in human volunteers.Conclusions: We provide evidence that ACE2 cleaves [Pyr1]apelin-13 to [Pyr1]apelin-13(1–12) and this cleavage product is expressed in human cardiovascular tissues. We have demonstrated biological activity of [Pyr1]apelin-13(1–12) at the human and rodent apelin receptor in vitro and in vivo. Our data show that reported enhanced ACE2 activity in cardiovascular disease should not significantly compromise the beneficial effects of apelin based therapies for example in PAH.

Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents.

BackgroundA family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise.ObjectiveTo test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.MethodsThe study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®).ResultsAt rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03).ConclusionNormotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.