Microvascular Vasodilation Research Articles

The Effect of Acute Sleep Extension on Blood Pressure Is Dependent on the Change in Sleep Efficiency.

The present study investigated the effect of acute sleep extension on blood pressure and microvascular vasodilation. Sleep and daily physical activity were objectively measured at home for two weeks using wrist actigraphy in 22 adults (60 ± 15 y). Vascular measurements were made in the morning on the 8th and 15th day. Participants spent at least 10 h in bed on the night prior to one of these testing days to extend sleep. Mean arterial blood pressure (MAP) and peak reactive hyperemia in the forearm were measured on each testing day. Reactive hyperemia and MAP were unaltered (p > 0.05) by sleep extension in the total sample. However, adults who experienced improved sleep efficiency with sleep extension (n = 10, 4.2 ± 1.4%) exhibited reduced MAP (-5.5 ± 4.6 mm Hg, p = 0.005) while adults who had little change or decreased sleep efficiency (n = 12, -1.7 ± 2.9%) showed no change in MAP. The reduction in MAP was significantly different between sleep efficiency groups (p = 0.005, Hedges' g = 1.21) after adjustment for sex and moderate-to-vigorous physical activity. The results of this study suggest that sleep extension has the potential to reduce blood pressure in midlife to older adults when the additional sleep time improves the quality of sleep.

Impaired microvascular insulin-dependent dilation in women with a history of gestational diabetes.

Women with a history of gestational diabetes mellitus (GDM) have a significantly greater lifetime risk of developing cardiovascular disease and type 2 diabetes compared with women who had an uncomplicated pregnancy (HC). Microvascular endothelial dysfunction, mediated via reduced nitric oxide (NO)-dependent dilation secondary to increases in oxidative stress, persists after pregnancy complicated by GDM. We examined whether this microvascular dysfunction reduces insulin-mediated vascular responses in women with a history of GDM. We assessed in vivo microvascular endothelium-dependent vasodilator function by measuring cutaneous vascular conductance responses to graded infusions of acetylcholine (10-10-10-1 M) and insulin (10-8-10-4 M) in control sites and sites treated with 15 mM l-NAME [NG-nitro-l-arginine methyl ester; NO-synthase (NOS) inhibitor] or 5 mM l-ascorbate. We also measured protein expression of total endothelial NOS (eNOS), insulin-mediated eNOS phosphorylation, and endothelial nitrotyrosine in isolated endothelial cells from GDM and HC. Women with a history of GDM had reduced acetylcholine (P < 0.001)- and insulin (P < 0.001)-mediated dilation, and the NO-dependent responses to both acetylcholine (P = 0.006) and insulin (P = 0.006) were reduced in GDM compared with HC. Insulin stimulation increased phosphorylated eNOS content in HC (P = 0.009) but had no effect in GDM (P = 0.306). Ascorbate treatment increased acetylcholine (P < 0.001)- and insulin (P < 0.001)-mediated dilation in GDM, and endothelial cell nitrotyrosine expression was higher in GDM compared with HC (P = 0.014). Women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and this attenuation is mediated, in part, by reduced NO-dependent mechanisms. Our findings further implicate increased endothelial oxidative stress in this microvascular insulin resistance.NEW & NOTEWORTHY Women who have gestational diabetes during pregnancy are at a greater risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. The mechanisms mediating this increased risk are unclear. Herein, we demonstrate that insulin-dependent microvascular responses are reduced in women who had gestational diabetes, despite the remission of glucose intolerance. This reduced microvascular sensitivity to insulin may contribute to increased cardiovascular disease and type 2 diabetes risk in these women.

Impaired microvascular function in patients with sickle cell anemia and leg ulcers improved with healing.

Leg Ulcer (LU) pathophysiology is still not well understood in sickle cell anaemia (SCA). We hypothesised that SCA patients with LU would be characterised by lower microvascular reactivity. The aim of the present study was to compare the microcirculatory function (transcutaneous oxygen pressure (TcPO2) on the foot and laser Doppler flowmetry on the arm) and several blood biological parameters between nine SCA patients with active LU (LU+) and 56 SCA patients with no positive history of LU (LU-). We also tested the effects of plasma from LU+ and LU- patients on endothelial cell activation. We observed a reduction of the TcPO2 in LU+ compared to LU- patients. In addition, LU+ patients exhibited lower cutaneous microvascular vasodilatory capacity in response to acetylcholine, current and local heating compared to LU- patients. Inflammation and endothelial cell activation in response to plasma did not differ between the two groups. Among the nine patients from the LU+ group, eight were followed and six achieved healing in 4.4 ± 2.5 months. Among thus achieving healing, microvascular vasodilatory capacity in response to acetylcholine, current and local heating and TcPO2 improved after healing. In conclusion, microcirculatory function is impaired in patients with LU, and improves with healing.

Hypertension Cure Research progress: The use of Zilebesiran in Hypertension

Chronic hypertension is a lifelong condition, and the patients need lifelong treatment with oral anti-hypertensive medications to say healthy and to prevent the development of serious complications. Demands for changing this situation of lifelong dependence on daily medications have been increasing. The aim of this paper is to highlight the recent breakthrough in hypertension research. Expert opinion: Zilebesiran, a small interfering RNA targeting angiotensinogen has the main advantage of long duration of action which allows meeting many hypertensions patients’ demand of avoiding the inconvenience of talking oral hypertensive medication on daily basis. It is worth mentioning that a more optimal blockade of renin-angiotensin-aldosterone system is not the only advantageous therapeutic approach for the treatment of hypertension. Impairment of endothelium-dependent vasodilation has been increasingly recognized as an important contributor for the development of essential hypertension’s-arginine is an amino acid that is considered the biological precursor of nitric oxide which is an important contributor to microvascular vasodilation and to the reduction atherosclerosis. Oral L-arginine has been emerging as a new effective approach of reducing blood through improving endothelial function in hypertensive patients.

Reduced systemic microvascular function in patients with resistant hypertension and microalbuminuria: an observational study.

Resistant hypertension (RH) may be associated with microalbuminuria (MAU), a marker of cardiovascular risk and target organ damage, and both may be related to microvascular damage. Laser speckle contrast imaging (LSCI) is an innovative approach for noninvasively evaluating systemic microvascular endothelial function useful in the context of RH with or without MAU. Microalbuminuria was defined as a urine albumin-to-creatinine ratio between 30 and 300 mg/g. Microvascular reactivity was evaluated using LSCI to perform noninvasive measurements of cutaneous microvascular perfusion changes. Pharmacological (acetylcholine [ACh], or sodium nitroprusside [SNP]) and physiological (postocclusive reactive hyperemia [PORH]) stimuli were used to evaluate vasodilatory responses. Thirty-two patients with RH and a normal urine albumin-to-creatinine ratio (RH group) and 32 patients with RH and microalbuminuria (RH + MAU) were evaluated. Compared with patients without MAU, patients with RH + MAU showed reduced endothelial-dependent systemic microvascular reactivity, as demonstrated by an attenuation of microvascular vasodilation induced by PORH. On the other hand, ACh-induced vasodilation did not differ between groups. The results also revealed reduced endothelial-independent (SNP-induced) microvascular reactivity in hypertensive patients with MAU compared with patients without MAU. In this study, there was evidence of endothelial dysfunction associated with impaired microvascular smooth muscle function in patients with RH + MAU. This may suggest that patients with RH need more intensive therapeutic strategies for the control of blood pressure to avoid further vascular damage and the resulting consequences.The study was registered at ClinicalTrials.gov ( https://register.clinicaltrials.gov ) under protocol # NCT05464849, initial release 12/07/2022.

Coronary microvascular dysfunction and autoregulatory capacity interfere with resting Dicrotic notch morphology

Coronary microvascular vasodilator capacity is substantially associated with coronary pressure waveform and dicrotic notch morphology, with or without concomitant epicardial disease. A prominent dicrotic notch is associated with preserved microvascular vasodilatory capacity and adequate resting microvascular tonus without relative hyperaemic state, cumulatively indicating a better microcirculatory health.

Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience

Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.

Donor plasma VEGF-A as a biomarker for myocardial injury and primary graft dysfunction after heart transplantation

BackgroundVascular endothelial growth factor (VEGF)-A is an angiogenic and proinflammatory cytokine with profound effects on microvascular permeability and vasodilation. Several processes may induce VEGF-A expression in brain-dead organ donors. However, it remains unclear whether donor VEGF-A is linked to adverse outcomes after heart transplantation. MethodsWe examined plasma VEGF-A levels from 83 heart transplant donors as well as the clinical data of these donors and their respective recipients operated between 2010 and 2016. The donor plasma was analyzed using Luminex-based Multiplex and confirmed with a single-target ELISA. Based on donor VEGF-A plasma levels, the recipients were divided into three equal-sized groups (low VEGF <500 ng/L, n=28; moderate VEGF 500-3000 ng/L, n=28; and high VEGF >3000 ng/L, n=27). Biochemical and clinical parameters of myocardial injury as well as heart transplant and kidney function were followed-up for one year, while rejection episodes, development of cardiac allograft vasculopathy, and mortality were monitored for five years. ResultsBaseline parameters were comparable between the donor groups, except for age, where median ages of 40, 45, and 50 were observed for low, moderate, and high donor plasma VEGF levels groups, respectively, and therefore donor age was included as a confounding factor. High donor plasma VEGF-A levels were associated with pronounced myocardial injury (TnT and TnI), a higher inotrope score, and a higher incidence of primary graft dysfunction in the recipient after heart transplantation. Furthermore, recipients with allografts from donors with high plasma VEGF-A levels had a longer length of stay in the intensive care unit and the hospital, and an increased likelihood for prolonged renal replacement therapy. ConclusionsOur findings suggest that elevated donor plasma VEGF-A levels were associated with adverse outcomes in heart transplant recipients, particularly in terms of myocardial injury, primary graft dysfunction, and long-term renal complications. Donor VEGF-A may serve as a potential biomarker for predicting these adverse outcomes and identifying extended donor criteria.

Central nervous system anomalies in 41 Chinese children incontinentia pigmenti

IntroductionIncontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase.Materials and methodsThis retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi’an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data.ResultsFourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 109), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 109). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration.ConclusionBrain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.

Central and peripheral cardiovascular responses after acute dietary nitrate supplementation in post-menopausal women

The transition to menopause is accompanied by augmented cardiovascular disease risk, partially attributed to reduced nitric oxide (NO) bioavailability. Despite a lower arterial stiffness than men, postmenopausal women are susceptible to increased aortic pulsatile hemodynamic load because of greater pressure wave reflection and vascular dysfunction. Increasing bioavailable NO with dietary nitrate has shown promise to reduce aortic (aSBP) and brachial (bSBP) systolic pressure healthy postmenopausal women. However, there are limited reports comparing hypertensive (HTN) and normotensive (NTN) postmenopausal women regarding wave separation analysis and vascular function following dietary nitrate supplementation. This study investigated if acute dietary nitrate supplementation would improve aortic hemodynamics, wave reflection characteristics, vascular stiffness, and vasodilatory function. We hypothesized that dietary nitrate would lower pulse wave velocity in hypertensives, lower aortic and brachial blood pressures and forward and backward wave magnitude and increase microvascular, but not macrovascular function in both groups. Fourteen postmenopausal women (n=7 HTN; n=7 NTN) participated in a two-day randomized crossover study design with dietary nitrate (nitrate rich, NR) or a placebo control (NP). Central and peripheral hemodynamics and carotid-femoral pulse wave velocity (cfPWV) were performed with a SphygmoCOR Excel, simultaneous resting macro- and- microvascular function was assessed using flow-mediated vasodilation (FMD) and post occlusive reactive hyperemia (PORH) using near-infrared spectroscopy. aSBP was reduced significantly following NR supplement within groups (HTN: NP 126±2 NR 120±1mmHg) and NTN group (NP 110± 1 NR 104±3mmHg p&lt;0.05). Forward pulse height HTN (NP 29±1.4 NR 26.3±1.4mmHg) NTN (NP 25.6±0.9 NR 24±2.7mmHg) and reflected pulse height HTN (NP 18.2±0.08 NR 17.2±0.4mmHg) NTN (NP 17.7±0.2 NR 15.7±1.07mmHg) were not different. cfPWV was faster in the HTN group and slowed with a NR supplement (HTN: NP 8.2±0.29 NR 7.4±0.31m/s; NTN NP 7.1±0.23 NR 6.6±0.62m/s p&lt;0.05). A significant interaction for %FMD was found (HTN: NP 7.3±0.8 NR 6.2±0.8%; NTN NP 6.6±0.7 NR 9.4±0.7%). Further, we found no difference in the NIRS derived microvascular function measurements (HTN: NP 1.9±0.2 NR 1.7±0.3%/s; NTN NP 1.6±0.1 NR 1.4±0.2%/s p&gt;0.05). These data indicate that dietary nitrate consumption led to a substantial reduction in aortic hemodynamics and reduced pulse wave velocity regardless of hypertension status. Interestingly, macrovascular, but not microvascular vasodilatory function was improved in the NTN women only. Dietary nitrate supplementation appears to have differential effects when considering HTN and NTN postmenopausal women. Supported with funds from The University of Wisconsin-La Crosse RSEL graduate grant. 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.

Mitochondrial and Microvascular Impairments in a Novel Swine Model of Peripheral Artery Disease

Introduction: Impaired skeletal muscle mitochondria and microvascular function have been reported in human peripheral artery disease (PAD). However, no large animal models of PAD have mimicked these impairments. Purpose: The purpose of this study was to examine the skeletal muscle microvasculature and mitochondria in a novel swine model of PAD. Hypothesis: We hypothesized that hindlimb ischemia leads to dysfunction of skeletal muscle microvessels and mitochondria. Methods: Ossabaw swine (n=5) with metabolic syndrome underwent endovascular coil occlusion of the right external iliac artery to generate hindlimb ischemia (ISC). The left leg served as a non-ischemic control (CON). After 4-weeks, biopsies were collected from both legs (lateral gastrocnemius). Skeletal muscle arterioles were assessed using video microscopy. Microvascular vasodilatory function was assessed in response to flow (Shear stress), acetylcholine (ACh), and sodium nitroprusside (SNP). Skeletal muscle mitochondrial function was assessed using high-resolution respirometry. Substrates were administered as follows: malate (M) &amp; glutamate (G), adenosine diphosphate (ADP), succinate (S), oligomycin, and ascorbate (Asc) &amp; N,N,N,N-tetramethyl-phenylenediamine (TMPD). Complex I state 2 (CI-S2) was assessed as M+G, complex I state 3 (CI-S3) was assessed as (M+G+ADP)-(M+G), complex II state 3 (CII-S3) was assessed as (M+G+ADP+S)-(M+G+ADP), complex I&amp;II state 3 (CI&amp;II S3) was assessed as (M+G+ADP+S)-(M+G), state 4 (S4) was assessed after oligomycin, and complex IV (CIV) respiration was assessed after Asc+TMPD. The respiratory control ratio (RCR) was calculated as CI&amp;II-S3/S4. Results: Vasodilation in response to flow was reduced in ISC vs. CON (Δ-13.1±13.7%, p=0.01). but not in response to ACh (Δ-6.2±17.7%, p=0.23) or SNP (Δ1.7±11.0%, p=0.53). Additionally, CI-S2 (Δ-0.3±3.7 pmolO2·s−1·mg−1, p=0.65), S4 (Δ-1.7±4.4 pmolO2·s−1·mg−1, p=0.14), and CIV (Δ-2.8±20.9 pmolO2·s−1·mg−1, p=0.65) were not different between ISC and CON. However, CI-S3 (Δ-4.7±5.0 pmolO2·s−1·mg−1, p&lt;0.01), CII-S3 (Δ-3.5±5.0 pmolO2·s−1·mg−1, p=0.02), CI&amp;II-S3 (Δ-8.5±8.7 pmolO2·s−1·mg−1, p&lt;0.01), and RCR (Δ-0.8±1.3 pmolO2·s−1·mg−1, p=0.04) were all reduced in ISC vs. CON. Conclusions: We found that skeletal muscle microvessels and mitochondria were impaired in our swine model. Based on the present findings, we conclude that our novel porcine model closely replicates the pathophysiology PAD, making it a promising large animal model for studying human PAD. This research was supported by the National Institutes of Health (R01HD106911, R01AG062198, R01AG0778031) and the Great Plains IdeA-CTR (U54 GM115458). 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.

The effect of acute estrogen suppression on cutaneous endothelium-dependent vasodilation in women with endometriosis

Cardiovascular disease risk is elevated in women with endometriosis and may be exacerbated by treatments that suppress estrogen. The purpose of this study was to determine the effects of acute estrogen suppression on endothelial function in women with endometriosis. We hypothesized that estrogen suppression would attenuate cutaneous endothelium-dependent vasodilation in endometriosis patients (ENDO; n = 2, 30 (1) y, 21.4 (0.2) kg·m2) but not in healthy controls (CON; n = 6, 28 (5) y, 24.9 (5.2) kg·m2). Trials were conducted with (POST) and without (PRE) 4 days of estrogen suppression (400 mg/day gonadotropin-releasing hormone antagonist, Elagolix®) during the first week of separate menstrual cycles. The cutaneous circulation was utilized as a model of microvascular vasodilatory function. Laser Doppler flowmetry was continuously measured during graded perfusions of acetylcholine through intradermal microdialysis (ACh, 1x10−10 – 1x10−1 M). Maximal vasodilation was elicited via 28 mM sodium nitroprusside perfusion and local heating (42°C). Cutaneous vascular conductance was calculated as LDF/mean arterial pressure (MAP). Dose response curves were generated with nonlinear modeling of normalized data with constraints and compared via median effective ACh dose (ED50) and HillSlope. Data are presented as mean (SD) and significance was set at α = 0.05. Baseline MAP was similar between trials for CON (PRE, 80.70 (6.32) mmHg; POST, 82.30 (5.37) mmHg; t[5] = -0.74, P = 0.49) and ENDO (PRE, 72.22 (0.31) mmHg; POST, 79.17 (7.31) mmHg; t[1] = -1.29, P = 0.42). ED50 was not impacted by estrogen suppression in CON (PRE, -3.61 (2.19) logM; POST, -2.80 (1.13) logM; t[5] = -1.04, P = 0.35) or ENDO (PRE, -3.08 (1.74); POST, -2.85 (0.68); t[1] = -0.13, P = 0.91). Similarly, HillSlope was not altered in CON (PRE, 1.00 (0.96); POST, 0.99 (1.14); t[5] = 0.01, P = 0.99) or ENDO (PRE, 0.81 (0.72); POST, 1.16 (1.15); t[1] = -0.26, P = 0.84). Acute estrogen suppression did not impact cutaneous endothelium-dependent vasodilation in healthy controls or women with endometriosis. A greater sample size will further evaluate this relationship. National Institutes of Health Grant 1R01HL161000. 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.

Divergent Vasodilator Mechanisms to Endothelial-Dependent Agonists with Advancing Age

Introduction: Microvascular function is maintained by a number of vasodilating factors, with nitric oxide (NO) and endothelial hyperpolarizing factors (EDHF) predominating. Advancing age is an independent risk factor in the development of cardiovascular disease, and NO-mediated vasodilation declines, or is unchanged, depending on the vascular bed examined, number of cardiovascular risk factors, or specific endothelial-dependent agonist used. Mechanisms contributing to cutaneous microvascular dysfunction with age have been attributed largely to reductions in NO signaling, but the role of EDHF-mediated dilation, particularly to acetylcholine (ACh), remains unclear. The purpose of this study was to determine the endothelial mechanisms contributing to age-induced cutaneous microvascular function and compare cutaneous microvascular function responses to those from isolated adipose arteriole preparations. We hypothesized that cutaneous microvascular vasodilation to ACh in older adults will be mediated primarily by EDHFs relative to young adults and that isolated adipose arteriole preparations will corroborate these findings. Methods: Four intradermal microdialysis fibers were placed in the skin of the ventral forearm of 9 young (3F/6M; 29±7 yrs) and 3 older adults (3F/0M; 59±11 yrs) for infusion of Ringer’s solution; L-NAME (10 mM), an NO synthase inhibitor; tetraethylammonium chloride (TEA; 50 mM), a non-specific K+ channel inhibitor; and a combination of L-NAME and TEA. Laser Doppler flowmetry and brachial mean arterial pressure were measured during infusion of ACh (10 mM and 100 mM) and in response to local heating to 39°C. Maximal vasodilation was assessed with heating to 43°C and infusion of sodium nitroprusside (28 mM). Adipose resistance arterioles for pressure myography were obtained from a gluteal biopsy or from surgical discard tissue, which were pre-constricted (ET-1), and ACh responses (10−9–10−4 M) were assessed in the presence of the above inhibitors. Cutaneous vascular conductance (CVC) and isolated arteriole responses are presented as % maximum vasodilation. Results: In response to local heating in young adults, L-NAME reduced vasodilator magnitude (Ringers 69.0±18.1% vs. L-NAME 30.3±12.1%; p&lt; 0.05) while TEA did not have any effect (69±18% vs. 49±28%; p=0.20). Combined L-NAME and TEA reduced vasodilation (69±18% vs. 19±6%; p&lt;0.05). Conversely, vasodilator magnitude to ACh was not different across the Ringers, L-NAME, or TEA sites (p=0.93-0.94), while combined inhibition of NOS and K+ channels with L-NAME and TEA, respectively, reduced vasodilator responsiveness (p&lt;0.05). In isolated resistance arterioles, there were no differences in %max dilation to ACh across inhibitor sites (p=0.19) in young adults. In older adults, neither independent nor combined inhibition of NOS or K+ channels impacted vasodilator responses to local heating, while vasodilator magnitude to ACh was most impacted by combined inhibition with L-NAME and TEA (83±14% vs. 32±15%; p&lt;0.05). Conclusion: Our data demonstrate that vasodilator plasticity in response to local heating is divergent with advancing age, relying on non-NO or K+ mechanisms relative to young adults, while NO and K+ mechanisms are suffcient to maintain ACh-mediated vasodilation. These findings further support the concept of diversity in vasodilator mechanisms within the microvasculature. NHLBI K99-HL161491 (WEH), K08-HL150340 (JJM), R01-HL160752 (JKF), R01-HL133029 (AB), and NICHD R01-HD099340 (MJD). 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.

High Intensity Interval Exercise Causes Acute Microvascular Dysfunction in Elderly Individuals with Low Cardiorespiratory Fitness - A Pilot Study

Background: Frailty is strongly associated with low physical and cardiorespiratory fitness, and unfortunately is observed in 20-50% of the ~50 million adults that experience surgical stress in the U.S. each year. The peripheral microvasculature may serve as a potential target to increase resilience to stress and improve postoperative outcomes. A better understanding of how the microvasculature responds to stress in elderly individuals with low fitness is thus needed. Objective: To define the relationship between cardiorespiratory fitness and microvascular resiliency to stress in elderly individuals. Hypothesis: Elderly individuals with low cardiorespiratory fitness will show acute reductions in acetylcholine (Ach)-mediated dilation of the skin microvasculature following the physiological stressful stimulus of high intensity interval exercise (HIIE). Methods: This was a prospective, observational study that enrolled elderly individuals aged 65-85 years from the community. Each participant was asked to complete two study visits. During visit 1, participants completed the Frailty Index and performed a graded cardiopulmonary exercise test (CPET) on a cycle ergometer with a metabolic cart to measure peak total body oxygen consumption (VO2 Peak). During visit 2, laser Doppler flowmetry with dermal microdialysis was performed on the ventral forearm to measure peak cutaneous microvascular vasodilation to Ach (10 mM). After baseline assessment, the participants performed a HIIE protocol where they repetitively switched between exercising at 70% of the peak workload achieved during the CPET for 60 seconds, followed by a 60 second active recovery at 10 watts. These intervals were repeated 12 times, for a total exercise duration of 24 min. Thirty minutes following exercise, Ach-mediated dilation of the cutaneous microvasculature was reassessed. Maximum dilator capacity of each site was assessed by infusing sodium nitroprusside (28 mM) and heating the skin to 43 °C. Results: Six individuals (1 male, 5 females; mean age 68 ±4 years) completed all study procedures. Based on age- and sex-predicted normative values for VO2 Max, three of the individuals had high physical fitness while three had low fitness (mean VO2 Peak = 27.5±1.1 vs. 13.6±3.4 ml/kg/min, respectively). Prior to HIIE there was no difference in peak dilation to Ach between the individuals with high vs. low fitness (% max dilation = 72±13 vs. 83±13, respectively). During HIIE, the individuals reached a Borg rating of perceived exertion of 15±4 (out of 20) and their peak heart rate was 74±15% of their age-predicted maximum. Ach-mediated dilation of the dermal microvasculature was reduced following HIIE in elderly individuals with low cardiorespiratory fitness (pre vs. post % maximum dilation = 82±13 vs. 49±27, respectively; mean change = -34±40 %) but unchanged in those with high fitness (pre vs. post % maximum dilation = 72±13 vs. 78±10, respectively; mean change = 5±3 %). Using Pearson correlation tests there was a strong correlation between the change in peak Ach-mediated dilation pre vs. post HIIE and both VO2 Peak (r=0.82, p=0.04) and Frailty Index score (r=-0.98, p&lt;0.001). Conclusion: Microvascular resilience to acute stress is decreased in elderly individuals with low cardiorespiratory fitness compared to those with high fitness. None. 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.

Antidepressant Treatment Preserves Microvascular Endothelium-Dependent Dilation in Women Who Have Had Preeclampsia

Women with a history of preeclampsia (hxPE) demonstrate persistent microvascular endothelial dysfunction which may contribute to the progression of cardiovascular disease. Women with hxPE also have higher rates of depression compared to women with a history of healthy pregnancy. Interestingly, accumulating evidence indicates that antidepressant treatment may have vasculoprotective effects and attenuate preeclampsia risk. However, whether antidepressant treatment impacts microvascular function in these women remains unknown. Therefore, we examined the effect of chronic antidepressant use on microvascular function in women with hxPE. We hypothesized that antidepressant-treated women with hxPE would have greater endothelium-mediated microvascular vasodilation than unmedicated women with hxPE. Five women with hxPE who were currently treated with an antidepressant (hxPE+AD; 36±3 years; 26±7 months postpartum), six who were not (hxPE-AD; 34±2 years; 26±5 months postpartum), and six unmedicated women with a history of uncomplicated pregnancy (HC; 37±1 years; 35±7 months postpartum) participated in one study visit. We measured cutaneous vascular conductance (CVC=laser doppler flowmetry flux/MAP) responses to graded perfusion of acetylcholine (10−10-10−1 mM) via microdialysis in a control (lactated Ringer's) site and a site treated with 15 mM NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthase inhibitor]. hxPE-AD had reduced endothelium-dependent dilation compared to HC (acetylcholine ³10−3 mM; P&lt;0.03). hxPE+AD had greater endothelium-dependent dilation compared to hxPE-AD (acetylcholine 10−2 and 10−3 mM; P&lt;0.02) and there were no differences between hxPE+AD and HC (all P&gt;0.05). L-NAME reduced endothelium-dependent dilation in all groups (all P&lt;0.001), and there was no difference between groups in NO-dependent dilation [area under the curve (AUC) at a control site − AUC at a L-NAME treated site; P=0.522]. These data suggest that microvascular endothelium-dependent dilation is preserved in women with a history of preeclampsia treated with an antidepressant, potentially mediated through non-NO-dependent mechanisms. Funding: American Heart Association CDA 937990. 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.

Acute effects of energy drink consumption on microvascular reactivity in young male volunteers at rest: a randomized trial.

Energy drinks are nonalcoholic beverages whose main ingredients are sugar, taurine, and caffeine. The consumption of energy drinks is increasing worldwide, but only a few conflicting studies have investigated the vascular effects of energy drinks in young adults. The aim of this study was to evaluate microvascular reactivity before and after energy drinks consumption in young healthy male volunteers. This was a cross-sectional prospective study. Microvascular reactivity signals were evaluated in the skin of the forearm using laser speckle contrast imaging with acetylcholine (ACh) iontophoresis before and 90 and 180 min after the randomized consumption of one ED or the same volume of water (control), followed by a postocclusive reactive hyperemia (PORH) test. Thirty-two volunteers were evaluated (age: 25.4±4.3 years). Energy drink consumption prevented the rest-induced reduction in cutaneous vascular conductance over time that was observed in the control group. In the control group, there were significant reductions in microvascular vasodilation at 90 and 180 min compared to baseline (P=0.004), but this was not the case in the energy drink group (P=0.76). Our results demonstrated that the reduction in microvascular conductance associated with prolonged immobility can be prevented by the consumption of one energy drink, highlighting the vasodilator effects of this beverage in young individuals at rest. The between-study variability in terms of the brand of energy drinks and the ingested volume, as well as the method of vascular evaluation and the inclusion criteria, may explain the discrepancies among previous studies on the vascular effects of energy drinks.

Patients with Chronic Coronary Syndrome Can Benefit from Consumption of Enriched Chicken Eggs: The Effects on Microvascular Function, Inflammatory Biomarkers, and Oxidative Status—Randomized Clinical Study

The aim of this clinical study was to determine the impact of the consumption of chicken eggs enriched with n-3 polyunsaturated fatty acids, selenium, vitamin E, and lutein on micro- and macrovascular endothelium-dependent dilation, inflammation biomarkers, and oxidative stress levels in participants with chronic coronary syndrome (CCS). This was a double-blind, placebo-controlled clinical study that included 30 CCS participants (9 women, 21 men) randomized into the control group (N = 15), who ate ordinary chicken eggs (three per day), and the Nutri4 group (N = 15), who ate enriched eggs (three per day) for 21 days. Microvascular and macrovascular endothelium-dependent vasodilation was evaluated by measuring forearm skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) and the flow-mediated dilation (FMD) of the brachial artery, respectively. The serum lipid profile, anti- and proinflammatory cytokine levels, serum concentration of nitric oxide synthase (NOS) isoforms, and oxidative stress biomarkers were measured before and after the diet protocols. Enriched, but not regular, chicken eggs significantly improved microvascular PORH and AChID and macrovascular FMD, increased the serum concentration of inducible NOS, decreased serum triglyceride levels, and decreased proinflammatory cytokine IL-17A and TGF-1β levels compared to initial measurements. Patients with CCS can benefit from the consumption of enriched chicken eggs due to improved lipid biomarkers, a more favorable anti-inflammatory milieu, and improved vascular relaxation at micro- and macrovascular levels.

Abstract 17927: Acipimox Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome

Introduction: Insulin resistance increases circulating free fatty acid (FFA) concentrations, which causes the release of inflammatory cytokines and induces endothelial dysfunction. Acipimox reduces FFA efflux and may improve insulin sensitivity and endothelium-dependent microvascular vasodilation. Hypothesis: We hypothesize that acipimox treatment will improve insulin-stimulated forearm blood flow (FBF) compared to placebo in volunteers with metabolic syndrome. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial (NCT00759291) evaluating 1-week of acipimox 250 mg QID on insulin-stimulated FBF in patients with and without metabolic syndrome. Results: Sixteen patients received acipimox (6 metabolic syndrome and 10 healthy controls). Patients with metabolic syndrome were older (63.8 vs 49.9 years old, p&lt;0.001) with higher baseline insulin levels (15.9 vs 3.5 μU/mL, p=0.002), and trended towards higher BMIs (30.9 vs 24.6 kg/m 2 , p=0.083). Baseline insulin sensitivity by Homeostatic Model Assessment for Insulin Resistance (HOMA IR) differed between controls and those with metabolic syndrome (0.68 vs 3.28, p=0.001) but did not change with acipimox (p=0.540, Panel A). Insulin stimulation increased FBF in patients treated with placebo (p=0.01, Panel B) and acipimox (p=0.03, Panel C) but was not augmented by acipimox in participants with metabolic syndrome or healthy controls (Panel D and E). In multivariable-adjusted regression analysis, acipimox did not increase FBF, even after adjusting for baseline FBF and key baseline differences, including metabolic syndrome. Conclusion: Acipimox did not improve insulin sensitivity and had no effect on microvascular endothelial dysfunction assessed by insulin-stimulated FBF. This suggests that FFA modulation does not reverse microvascular dysfunction in patients with metabolic syndrome.

Enhanced Microvascular Adaptation to Acute Physical Stress and Reduced Oxidative Stress in Male Athletes Who Consumed Chicken Eggs Enriched with n-3 Polyunsaturated Fatty Acids and Antioxidants-Randomized Clinical Trial.

This randomized interventional study aimed to determine the effects of n-3 polyunsaturated fatty acids, selenium, vitamin E, and lutein supplementation in the form of enriched chicken egg consumption on microvascular endothelium-dependent vasodilation, oxidative stress, and microvascular response to an acute strenuous training session (ASTS) in competitive athletes. Thirty-one male athletes were assigned to a control (n = 17) or a Nutri4 group (n = 14) who consumed three regular or enriched chicken eggs per day, respectively, for 3 weeks. Significantly enhanced endothelium-dependent responses to vascular occlusion (PORH) and iontophoresis of acetylcholine (AChID) were observed in the Nutri4 group but not in the control group after egg consumption. Formation of peroxynitrite and hydrogen peroxide in peripheral blood mononuclear cells, as well as serum concentration of 8-iso prostaglandin F2α, decreased in the Nutri4 group while remaining unchanged in controls. PORH and AChID were reduced post-ASTS compared with pre-ASTS, both before and after the diets, in both groups. However, the range of PORH responsiveness to ASTS (ΔPORH) increased after consumption of enriched eggs. These results suggest that consumption of enriched chicken eggs has a beneficial effect on microvascular endothelium-dependent vasodilation and the reduction of oxidative stress levels in competitive athletes. Also, microvascular adaptation to the ASTS was improved after consumption of Nutri4 eggs.

Sex Differences in Oxidative Stress-Mediated Reductions in Microvascular Endothelial Function in Young Adult e-Cigarette Users.

Chronic electronic-cigarette (EC) use is reported to decrease vascular endothelial function. However, the mechanism(s) mediating this reduction remain unclear. In this study, we examined endothelium- and NO-dependent dilation, and the role of oxidative stress in attenuating these responses, in healthy young EC users (n=20, 10 males/10 females) compared with healthy controls (n=20, 10 males/10 females). We hypothesized that EC would have reduced endothelium- and NO-dependent dilation and administration of the superoxide scavenger tempol would increase these responses in EC. We further hypothesized that female EC would have the greatest reductions in endothelium- and NO-dependent dilation. We assessed microvascular endothelium-dependent vasodilator function in vivo by measurement of cutaneous vascular conductance (%CVCmax) responses to a standardized local heating protocol in control and 10 μM tempol-treated sites. After full expression of the local heating response, 15 mM NG-nitro-L-arginine methyl ester (NO synthase inhibition) was perfused. EC had significantly reduced endothelium- (73±15 versus 87±9%CVCmax; P<0.001) and NO-dependent (48±17% versus 62±15%; P=0.011) dilation. Tempol perfusion increased endothelium-dependent (84±12%CVCmax P=0.01) and NO-dependent (63±14% P=0.005) dilation in EC but had no effect in healthy control. Within female sex, EC had lower endothelium-dependent (71±13 versus 89±7%CVCmax; P=0.002) and NO-dependent (50±6 versus 69±11%; P=0.005) dilation compared with healthy control, and tempol augmented endothelium-dependent (83±13%CVCmax; P=0.002) and NO-dependent (62±13%; P=0.015) dilation. There were no group or treatment differences within male sex. Healthy young adult EC users have reduced microvascular endothelium-dependent and NO-dependent dilation, driven by greater reductions in female EC users, and mediated in part by superoxide.