Larger Decrease In Blood Pressure Research Articles

Engagement in mHealth-Prompted Self-Measured Blood Pressure Monitoring Among Participants Recruited From a Safety-Net Emergency Department: Secondary Analysis of the Reach Out Trial.

Hypertension, a key modifiable risk factor for cardiovascular disease, is more prevalent among Black and low-income individuals. To address this health disparity, leveraging safety-net emergency departments for scalable mobile health (mHealth) interventions, specifically using text messaging for self-measured blood pressure (SMBP) monitoring, presents a promising strategy. This study investigates patterns of engagement, associated factors, and the impact of engagement on lowering blood pressure (BP) in an underserved population. We aimed to identify patterns of engagement with prompted SMBP monitoring with feedback, factors associated with engagement, and the association of engagement with lowered BP. This is a secondary analysis of data from Reach Out, an mHealth, factorial trial among 488 hypertensive patients recruited from a safety-net emergency department in Flint, Michigan. Reach Out participants were randomized to weekly or daily text message prompts to measure their BP and text in their responses. Engagement was defined as a BP response to the prompt. The k-means clustering algorithm and visualization were used to determine the pattern of SMBP engagement by SMBP prompt frequency-weekly or daily. BP was remotely measured at 12 months. For each prompt frequency group, logistic regression models were used to assess the univariate association of demographics, access to care, and comorbidities with high engagement. We then used linear mixed-effects models to explore the association between engagement and systolic BP at 12 months, estimated using average marginal effects. For both SMBP prompt groups, the optimal number of engagement clusters was 2, which we defined as high and low engagement. Of the 241 weekly participants, 189 (78.4%) were low (response rate: mean 20%, SD 23.4) engagers, and 52 (21.6%) were high (response rate: mean 86%, SD 14.7) engagers. Of the 247 daily participants, 221 (89.5%) were low engagers (response rate: mean 9%, SD 12.2), and 26 (10.5%) were high (response rate: mean 67%, SD 8.7) engagers. Among weekly participants, those who were older (>65 years of age), attended some college (vs no college), married or lived with someone, had Medicare (vs Medicaid), were under the care of a primary care doctor, and took antihypertensive medication in the last 6 months had higher odds of high engagement. Participants who lacked transportation to appointments had lower odds of high engagement. In both prompt frequency groups, participants who were high engagers had a greater decline in BP compared to low engagers. Participants randomized to weekly SMBP monitoring prompts responded more frequently overall and were more likely to be classed as high engagers compared to participants who received daily prompts. High engagement was associated with a larger decrease in BP. New strategies to encourage engagement are needed for participants with lower access to care.

Prenatal exercise and cardiovascular health (PEACH) study: impact of acute and chronic exercise on cerebrovascular hemodynamics and dynamic cerebral autoregulation.

We performed a randomized controlled trial measuring dynamic cerebral autoregulation (dCA) using a sit-to-stand maneuver before (SS1) and following (SS2) an acute exercise test at 16-20 wk gestation (trimester 2, TM2) and then again at 34-37 wk gestation (third trimester, TM3). Following the first assessment, women were randomized into exercise training or control (standard care) groups; women in the exercise training group were prescribed moderate intensity aerobic exercise for 25-40 min on 3-4 days per week for 14 ± 1 wk. Resting seated mean blood velocity in the middle cerebral artery (MCAvmean) was lower in TM3 than in TM2 but not impacted by exercise training intervention. No metric of dCA was impacted by gestational age or exercise training during SS1. During SS2, there were greater absolute and relative decreases in mean arterial blood pressure (MAP) and MCAvmean, but this was not impacted by the intervention. There was also no difference in the relationship between the decrease in MCAvmean compared with the decrease in MAP (%/%) or the onset of the regulatory response with respect to acute exercise, gestational age, or intervention; however, rate of regulation was faster in women in the exercise group following acute exercise (interaction effect, P = 0.048). These data highlight the resilience of the cerebral circulation in that dCA was well maintained or improved in healthy pregnant women between TM2 and TM3. However, future work addressing the impact of acute and chronic exercise on dCA in women who are at risk for cardiovascular complications during pregnancy is needed.NEW & NOTEWORTHY These data represent the first assessments of dynamic cerebral autoregulation in pregnancy using a sit-to-stand. We used a randomized controlled trial to show dynamic cerebral autoregulation is not impacted by gestational age or by chronic exercise. However, there are larger decreases in blood pressure and cerebral blood velocity following sit-to-stand after acute exercise without adverse events. These data highlight the adaptability of the cerebral circulation during pregnancy to accommodate large changes in the cardiovascular system.

Proteinase-activated receptor-2 (PAR2) on blood pressure and electrolyte handling in the late pregnant rat.

What is the central question of this study? Pregnancy requires marked renal sodium and potassium retention and cumulative plasma volume expansion, in the setting of reduced blood pressure. Research in male rodents has shown that activation of PAR2 can produce peripheral vasodilatation, stimulate renal sodium chloride reabsorption and inhibit renal potassium secretion. Here, we investigate PAR2 activation in virgin and normal pregnant rats. What is the main finding and its importance? PAR2 expression and sensitivity to activation are increased in pregnancy. This implicates a possible role for PAR2 in supporting the renal/vascular adaptations of pregnancy required for normal maternal plasma volume expansion. A healthy pregnancy involves renal and systemic haemodynamic adaptations, which allow renal sodium and potassium retention and cumulative plasma volume expansion, accompanied by a decline in blood pressure attributable to a reduction in the total peripheral vascular resistance. When these adaptations do not occur, pregnancy is compromised. The mechanisms permitting these opposing adaptations are largely unknown. Research in male rodents has shown that activation of PAR2 can produce peripheral vasodilatation, stimulate renal sodium chloride reabsorption and inhibit renal potassium secretion. Here, we investigate PAR2 activation in female virgin and normal late pregnant (LP) rats. We measured the mRNA expression of PAR2 in the renal cortex, outer medulla and inner medulla of virgin and LP rats using quantitative real-time PCR. We also measured in vivo blood pressure, natriuretic and kaliuretic responses to PAR2-activating peptide (SLIGRL-NH2 ) in anaesthetized virgin and LP rats. We found that PAR2 mRNA was increased in the inner medulla of LP rats. We also found that LP rats had larger decreases in blood pressure and increases in net sodium retention compared with virgin rats. These findings suggest that pregnancy enhances sensitivity to the blood pressure-lowering and sodium-retaining effects of PAR2.

BDNF Augments NMDA‐signaling and Reduces GABAA‐signaling in the Paraventricular Nucleus of the Hypothalamus (PVN) to Elevate Blood Pressure

PVN presympathetic neurons, projecting to the rostral ventrolateral medulla (RVLM) or the spinal cord, play a critical role in the regulation of blood pressure. BDNF is a neurotrophic factor known to be upregulated in the PVN in response to hypertensive stimuli such as stress. However, the mechanisms by which BDNF modulates cardiovascular regulation in the PVN remains unclear. BDNF alters glutamatergic and GABAergic signaling, as well as neuronal morphology broadly in the central nervous system. Within the PVN, glutamatergic synaptic input and NMDA‐signaling are elevated, while GABAergic inhibition is reduced in hypertensive models. We tested the hypothesis that increased BDNF expression in the PVN elevates blood pressure by enhancing NMDA‐signaling, diminishing GABAA‐signaling and altering morphology of RVLM‐projecting PVN neurons. To simulate stress‐related upregulation of BDNF in the PVN, an AAV2 viral vector expressing BDNF was bilaterally injected into the PVN of Sprague Dawley rats, while control rats received AAV2‐GFP injections. Three weeks later, blood pressure and heart rate responses to PVN injections of NMDA and GABAA agonists and antagonists were recorded under anesthesia. Our results showed that inhibition of NMDA receptors with AP5 induced significantly larger decreases in blood pressure and heart rate in the BDNF group (−23±4 mmHg and −56±17 BPM) compared with the GFP group [5±1 mmHg (p<0.01) and −5±1 BPM (p<0.05)]. In contrast, activation of NMDA receptors with NMDA induced similar cardiovascular responses in GFP and BDNF animals. Inhibition of GABAA receptors with gabazine induced significantly smaller blood pressure increases in the BDNF group (32±6 mmHg) compared to GFP (61±11 mmHg, p<0.05), but heart rate responses were similar in the two groups. Activation of GABAA receptors with muscimol caused significantly reduced hypotensive responses in the BDNF group (−14±2 mmHg) compared to GFP (−23±4 mmHg, p<0.05), while changes in heart rate were similar. Quantitative RT‐PCR from PVN brain punches indicated that expression of NMDAR1 or GABAA‐Δ was unaffected by BDNF overexpression. However, immunofluorescence imaging in PVN brain sections demonstrated that BDNF significantly increased the soma size of RVLM‐projecting PVN neurons. In summary, our findings indicate that BDNF augments glutamate signaling in the PVN, primarily by increasing presynaptic glutamate release, and reduces GABA inhibition possibly through postsynaptic mechanisms. Finally, BDNF may also affect the balance of excitatory/inhibitory synaptic balance and regulation of blood pressure by increasing the soma size of PVN‐RVLM neurons.Support or Funding InformationR01 HL133211‐01A1.

Device-guided slow breathing reduces blood pressure and sympathetic activity in young normotensive individuals of both sexes.

Slow breathing (SLOWB) is recommended for use as an adjuvant treatment for hypertension. However, the extent to which blood pressure (BP) responses to SLOWB differ between men and women are not well-established. Therefore, we tested the hypothesis that an acute bout of SLOWB would induce larger decreases in BP in males than in females, given that males typically have higher resting BP. We also examined autonomic contributors to reduced BP during SLOWB; that is, muscle sympathetic nerve activity and spontaneous cardiovagal (sequence method) and vascular sympathetic baroreflex sensitivity. We tested normotensive females (n = 10, age: 22 ± 2 y, body mass index: 22 ± 2 kg/m2) and males (n = 12, age: 23 ± 3 y, body mass index: 26 ± 4 kg/m2). Subjects were tested at baseline and during the last 5 min of a 15-min RESPeRATE-guided SLOWB session. Overall, SLOWB reduced systolic BP by 3.2 ± 0.8 mmHg (main effect, P < 0.01). Females had lower systolic BP (main effect, P = 0.02); we observed no interaction between sex and SLOWB. SLOWB also reduced muscle sympathetic nerve activity burst incidence by -5.0 ± 1.4 bursts/100 heartbeats (main effect, P < 0.01). Although females tended to have lower burst incidence (main effect, P = 0.1), there was no interaction between sex and SLOWB. Cardiovagal baroreflex sensitivity improved during SLOWB (21.0 vs. 36.0 ms/mmHg, P = 0.03) with no effect of sex. Despite lower overall BP in females, our data support a lack of basement effect on SLOWB-induced reductions in BP, as SLOWB was equally effective in reducing BP in males and females. Our findings support the efficacy of the RESPeRATE device for reducing BP in both sexes, even in young, normotensive individuals.NEW & NOTEWORTHY We provide support for the effectiveness of device-guided slow breathing for blood pressure reduction in young normotensive women and men. Despite having lower baseline blood pressure and sympathetic nerve activity, women experienced equivalent reductions in both measures in response to RESPeRATE-guided slow breathing as men. Thus, slow breathing appears to be effective in young healthy normotensive individuals of both sexes and may be an ideal preventative therapy against future hypertension.

Blood Pressure Responses to Slow Breathing in Young Healthy Individuals: Is there an Effect of Sex?

Slow breathing has been recommended by the American Heart Association as an effective adjunctive approach for the treatment of hypertension. RESPeRATE is an FDA‐approved device that guides the user into a slow breathing pattern, sensitizing the baroreflex and thus acutely reducing blood pressure (BP). Limited research has demonstrated the effectiveness of this device in inducing sustained reductions in BP in older adults with hypertension. However, whether responsiveness to device‐guided slow breathing is affected by sex remains unknown. Therefore, the purpose of this study was to compare the effectiveness of the RESPeRATE device in acutely reducing BP between women and men. We hypothesized that slow breathing would result in larger decreases in BP in men than in women, given that men typically have higher resting blood pressure than women. We examined BP at baseline and during the last minute of a 15‐min slow breathing session guided by the RESPeRATE device in 9 young healthy subjects: 5 women (mean±SD age: 23±1 y, BMI: 22±1 kg/m2) and 4 men (mean±SD age: 24±2 y, BMI: 26±6 kg/m2). There were no differences in age (p=0.8) or BMI (p=0.2) between groups. We assessed the effects of sex and slow breathing on mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) using two‐way ANOVAs. Compared to men, women had lower resting MAP (77±4 vs. 87±7 mmHg; p=0.03) and DBP (64±3 vs 77±6 mmHg; p&lt;0.01) with a trend towards lower SBP (103±4 vs 110±9 mmHg; p=0.1). Respiration rate was similar between sexes at rest (women: 15±4 breaths/min, men: 13±3; p=0.4). Respiration rate decreased during slow breathing (−7.4±1.6 breaths/min, main effect of slow breathing: p&lt;0.01) with no effect of sex (p=0.4). Slow breathing was associated with reduced MAP (women: 68±12 mmHg, men: 79±10; main effect of slow breathing: p=0.02, effect of sex: p=0.1), SBP (women: 93±21 mmHg, men: 96±17; main effect of slow breathing: p=0.04, effect of sex: p=0.6), and DBP (women: 56±10 mmHg, men: 69±8; main effect of slow breathing: p&lt;0.01). However, we observed a significant effect of sex on DBP (p&lt;0.01), as women maintained lower DBP than men during slow breathing. In conclusion, the RESPeRATE device acutely reduced BP in young healthy individuals, and these effects were consistent in both women and men. That is, despite women starting at lower resting BPs, slow breathing was equally effective in reducing BP in young healthy women and men. Our results provide preliminary support for the efficacy of the RESPeRATE device as an intervention to reduce blood pressure in young healthy individuals of both sexes.Support or Funding InformationThis project was supported by a Natural Sciences and Engineering Research Council Discovery Grant (CWU). TEA &amp; YC were supported by the McGill Department of Kinesiology and Physical Education Graduate Excellence Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluating Cardiorespiratory Responses to Slow Breathing in Young Healthy Individuals: FitBit “Relax Mode” versus RESPeRATE

Device‐guided slow breathing has been tested in clinical populations (e.g., hypertension, type II diabetes) with the goal of reducing blood pressure (BP) via a sensitization of the baroreflex. The FitBit's “Relax Mode” and the RESPeRATE device are commercially available devices which acutely reduce an individual's respiration rate and, by extension, BP. To the best of our knowledge no studies have directly compared the cardiorespiratory effects of these devices. The purpose of this study was to compare acute respiratory and BP responses to the RESPeRATE device (RESP), the FitBit's Relax Mode (FB). We hypothesized that RESP would result in greater decreases in respiratory rate than FB, leading to larger decreases in BP. We evaluated the responses to a single bout of RESP (15 min) and FB (5 min) in young (mean±SD age: 23±1 y), healthy (BMI: 23±3 kg/m2; mean arterial BP [MAP]: 82±8 mmHg) individuals (n=2 men, n=3 women). To normalize the duration of the stimuli, we compared the mean of the responses to FB to the mean of the last 5 min of RESP; the order of devices was randomized between subjects. Both devices were effective in reducing respiration rate from baseline (RESP: 11.1±3.5 to 5.6±0.7 breaths/min; FB: 11.2±1.8 to 7.3±0.3; main effect of slow breathing: p&lt;0.01; effect of device: p=0.4). In contrast, tidal volume expansion increased from baseline during slow breathing (RESP: 0.70±0.33 to 1.41±0.50 L; FB: 0.61±0.17 to 1.20±0.59; main effect of slow breathing: p&lt;0.01; effect of device: p=0.6). However, there was no change in minute ventilation from baseline levels (RESP: 7.0±1.8 to 7.8±3.0 L/min; FB: 6.7±1.8 to 8.7±4.2; main effect of slow breathing: p=0.1; effect of device: p=0.9), suggesting that the subjects did not hyperventilate during either slow breathing condition. MAP decreased from baseline during slow breathing (RESP: 82±8 to 80±8 mmHg; FB: 82±8 to 81±7; main effect of slow breathing: p=0.01; effect of device: p=0.9). Conversely, a significant slow breathing by device interaction (p=0.05) revealed that diastolic BP (DBP) was reduced from baseline only in the RESP condition (69±7 to 67±8 mmHg, p&lt;0.01); FB was not associated with a reduction in DBP (69±8 to 69±8 mmHg, p=0.2). Our preliminary data indicated that while RESP reduced respiratory rate similarly to the FB, RESP may be more effective than FB at acutely reducing DBP in young healthy adults.Support or Funding InformationThis project was supported by a Natural Sciences and Engineering Research Council Discovery Grant (CWU). TEA &amp; YC were supported by the McGill Department of Kinesiology and Physical Education Graduate Excellence Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A17995 Value-based assessment of blood pressure telemonitoring in hypertensive patients

Objectives: To investigate whether BPTM fits all three principles of value-based approach: clinical benefit, cost-effectiveness and improved patient reported outcome/experience measures (PROMs/PREMs). Methods: Study included 190 ambulatory patients (137 males, mean age 51 ± 17 years) with uncontrolled HTN assigned to BPTM group (110 patients) and usual care group (UC, 80 patients). Both groups had baseline and 3-months follow-up clinic visits. Between visits BPTM patients used simple, secure web-platform allowing physician-patient communication, storage and blood pressure (BP) and medication data exchange. Clinical efficacy endpoints included BP changes and BP target rate. Economic evaluation settled in Euro currency consisted of cost of illness (COI), incremental cost-effectiveness ratio (ICER); cost-utility analysis (CUA) was performed using generic PROM (SF-36). PREMs collection via PEQ chart. Results: BPTM group characterized by significantly larger decrease in BP (−16 ± 6 mmHg SBP,p = 0,005; − 8,4 ± 3,4 mmHg DBP,p = 0,02) while the number of antihypertensive drugs remained unchanged (+0,3 drugs in BPTM group; p = 0,15). COI was x2.36 higher in BPTM (196.9 € vs 83.5 €, p < 0.005) and ICER was 8.45 €/mmHg/patient (95% CI €4,9–12). BPTM improved PROMs (+2.9 for PH-SF-36,p = 0.04) with 0,06 quality adjusted life years (QALYs) gained. Resultant CUA for BPTM was 2698 €/QALY/patient at a willingness-to-pay threshold of 20383 €/QALY. PREMs improved (+10 points,p = 0,01). UC showed minor QoL changes (+1,3 in PH-SF-36,p = 0,56; +6 PEQ, p = 0,03). No association between BP and QoL results (P = 0,5 for all). Conclusion: BPTM being cost-effective and cost-saving tool incorporates both clinical benefits with the patient-perceived value.

P 38 Proteinase activated receptor 2 (PAR2) on blood pressure and electrolyte handling in the normal pregnant rat

Objectives Healthy pregnancy is characterized by avid aldosterone-mediated renal sodium retention driving a ∼40% plasma volume expansion in the presence of decreased or normal blood pressure. Incredibly, gestational potassium retention occurs in the face of this high circulating aldosterone, decreased renal NCC abundance/ phosphorylation, and increased renal ENaC activity, all of which are potent kaliuretic factors. The mechanisms permitting these opposing adaptations are largely unknown. Research in non-pregnant rats has shown that activation of proteinase activated receptor type 2 (PAR2) can produce vasodilation, inhibit potassium secretion via the renal outer medullary potassium channel (ROMK) in principal cells, and stimulate thiazide sensitive sodium chloride reabsorption (pendrin/NDCBE-mediated) in intercalated cells of the cortical collecting duct. Here, we investigate renal PAR2 activation in virgin and normal pregnant rats. Methods We measured the mRNA expression of PAR2 in the renal cortex, outer medulla, and inner medulla of virgin (V), mid- (MP), and late pregnant (LP) rats using quantitative real-time PCR. We also measured in vivo blood pressure (BP), natriuretic, and kaliuretic responses to 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg doses of PAR2 agonist peptide (SLIGRL-NH2) in anesthetized V and LP rats. Results We found that PAR2 mRNA was increased in the inner medulla of MP and LP rats. We also found that LP rats had larger decreases in BP compared to baseline than V rats at 0.1 and 0.3 mg/kg doses of agonist peptide. LP rats also had increased net sodium retention compared to virgin rats following 0.3 mg/kg and 1 mg/kg agonist peptide, but decreased net potassium retention compared to virgins with all doses. Conclusions PAR2 mRNA (an index of activity) is increased in the pregnant rat and activation of this receptor causes larger decreases in BP and increases in sodium retention compared to virgin controls. Further studies will determine the mechanism involved as well as the physiological role of increased renal PAR2 in pregnancy.

Factors Predicting the Fall in Clinic Blood Pressure on Repeated Measurements

Abstract Aim Clinic blood pressure (BP) readings tend to decrease towards the true value on repeated measurements. We aimed to identify factors associated with the fall in systolic and diastolic BP on repeated measurements. Methods We used BP data on 4943 participants aged ≥20 (2475 men, 2468 women; mean age±SD, 50±18 years) in the United States National Health and Nutrition Examination Survey (NHANES) 2007-8. Repeated measurements analysis of variance was used to identify predictors of the change in BP with time. Results As expected, BP was significantly related to age, gender and body mass index (P&lt;0.001). Both systolic and diastolic BP decreased significantly with time (P&lt;0.001). These decreases were significantly related to age and the maximum cuff pressure (P&lt;0.001). They were not related to body weight, arm dimension, triceps skinfold thickness, cuff size, and consumption of food, coffee and tobacco in the preceding 30 minutes. Conclusion Older persons and those with high systolic BP had larger decreases in BP on repeated measurements. Hence, adequate inflation of cuff and repeated measurements in the elderly are key factors for measuring clinic BP accurately.

Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade.

Non-synonymous GRK4 variants, R65L, A142V and A486V, are associated with essential hypertension in diverse populations. This study replicated the association of GRK4 variants, including GRK4(142V), with human essential hypertension in a Japanese population (n=588; hypertensive, n=486 normotensive controls) and determined whether the presence of GRK4 variants predicted the blood pressure (BP) response to angiotensin receptor blockers (ARBs) in patients with essential hypertension. We analyzed 829 patients and compared the response to ARBs between individuals with no GRK4 variants (n=136) and those with variants at one or any of the three loci (n=693). Carriers of hGRK4(142V) had a greater decrease in systolic BP in response to ARBs than non-carrier hypertensive patients. By contrast, those with variants only at GRK4(486V) were less likely to achieve the BP goal in response to an ARB than those with no variants. These studies showed for the first time the association between GRK4(142V) and a larger decrease in BP with ARBs in hypertensive patients.

Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats

Oxidative stress and suppressed H2S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H2S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n = 6) were treated for 4 weeks either as controls or received NaHS (SHR + NaHS), tempol (SHR + Tempol), or NaHS plus tempol (SHR + NaHS + Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0 ± 2 vs. 100.0 ± 3 mmHg), lower plasma and urinary H2S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p < 0.05). Treatment either with NaHS or with tempol alone decreased blood pressure and oxidative stress and improved renal hemodynamic and excretory function compared to untreated SHR. Combined NaHS and tempol therapy in SHRs caused larger decreases in blood pressure (∼20–22% vs. ∼11–15% and ∼10–14%), increases in creatinine clearance, urinary sodium excretion and fractional sodium excretion and up-regulated the antioxidant status compared to each agent alone (all p < 0.05). These findings demonstrated that H2S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.

Breastfeeding and Cardiometabolic Profile in Childhood

Although the observed association between breastfeeding and cardiometabolic profile in childhood and adolescence in previous studies has biological plausibility, the precise mechanism and magnitude remain far from being fully understood.1 Early nutrition and epigenetic programming,2 anti-inflammatory properties,3 and cardiorespiratory fitness4 are among numerous hypotheses that are currently being actively investigated. In this issue of Circulation, Martin et al5 report on this subject. Their intervention study began in 1996 to 1997 in 31 Belarussian maternity hospitals and affiliated outpatient clinics with an enrollment of 17046 breastfeeding mothers of healthy term infants. The trial was originally designed to assess the effects of a breastfeeding promotion and support intervention on duration of breastfeeding. Duration of both exclusive (infant only receives breast milk without any additional food or drink, not even water) and any breastfeeding (includes nonexclusive and exclusive) was assessed in the intervention and nonintervention groups.6 The planned 11.5-year follow-up of ≈80% of study participants who had fasted for the follow-up assessment and did not have diabetes mellitus allowed the authors to test whether an intervention to improve breastfeeding duration and exclusivity also influenced cardiometabolic risk factors in childhood. No significant differences between the intervention and control groups were found in levels of blood pressure, fasting insulin, adiponectin, glucose, apolipoprotein A1, or metabolic syndrome.

Therapeutic use of coconut water

This paper is a review about therapeutic use of coconut water. We began with its chemical composition, pointing that it is reach in antioxidants, potassium, calcium, carbohydrates, and poor in sodium. The antioxidant activity from coconut water is of interest as a potential natural food antioxidant additive, a nutraceutical. When coconut water is used in hypertensive people, this brought about a large decrease in blood pressure, including increased frequency in urination suggest a possible diuretic action. Additionally, in all cases of persons consuming coconut water on a regular basis an increase in the plasma level of potassium is observed. This would be a contributing factor in the decreases in blood pressure, suggesting a potassium sparing natriuretic. Some time trial tests as the measure of exercise performance have determined the efficacy of coconut water and other beverages on enhancing hydration and performance following dehydrating exercise. In conclusion, coconut water can be used in cases of hypertension, rehydration in sports, together with early refeeding, as a home glucose electrolyte oral rehydration solution in the early stages of mild diarrhoeal disease, despite not having a balanced electrolyte composition. However, it should not be used in patients with severe diarrhoea, or in patients who are severely dehydrated and/or in whom renal function is impaired. Further studies should be conducted to better understand the effects of coconut water as a therapeutic agent.

Impact of Resistance Training on Blood Pressure and Other Cardiovascular Risk Factors

We reviewed the effect of resistance training on blood pressure and other cardiovascular risk factors in adults. Randomized, controlled trials lasting ≥4 weeks investigating the effects of resistance training on blood pressure in healthy adults (age ≥18 years) and published in a peer-reviewed journal up to June 2010 were included. Random- and fixed-effects models were used for analyses, with data reported as weighted means and 95% confidence limits. We included 28 randomized, controlled trials, involving 33 study groups and 1012 participants. Overall, resistance training induced a significant blood pressure reduction in 28 normotensive or prehypertensive study groups [-3.9 (-6.4; -1.2)/-3.9 (-5.6; -2.2) mm Hg], whereas the reduction [-4.1 (-0.63; +1.4)/-1.5 (-3.4; +0.40) mm Hg] was not significant for the 5 hypertensive study groups. When study groups were divided according to the mode of training, isometric handgrip training in 3 groups resulted in a larger decrease in blood pressure [-13.5 (-16.5; -10.5)/-6.1(-8.3; -3.9) mm Hg] than dynamic resistance training in 30 groups [-2.8 (-4.3; -1.3)/-2.7 (-3.8; -1.7) mm Hg]. After dynamic resistance training, Vo(2) peak increased by 10.6% (P=0.01), whereas body fat and plasma triglycerides decreased by 0.6% (P<0.01) and 0.11 mmol/L (P<0.05), respectively. No significant effect could be observed on other blood lipids and fasting blood glucose. This meta-analysis supports the blood pressure-lowering potential of dynamic resistance training and isometric handgrip training. In addition, dynamic resistance training also favorably affects some other cardiovascular risk factors. Our results further suggest that isometric handgrip training may be more effective for reducing blood pressure than dynamic resistance training. However, given the small amount of isometric studies available, additional studies are warranted to confirm this finding.

Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism

Surgically correctable forms of primary aldosteronism are characterized by unilateral aldosterone hypersecretion and renin suppression, associated with varying degrees of hypertension and hypokalemia. Unilateral aldosterone hypersecretion is caused by an aldosterone-producing adenoma (also known as Conn's adenoma and aldosteronoma), primary unilateral adrenal hyperplasia and rare cases of aldosterone-producing adrenocortical carcinoma. In these forms, unilateral adrenalectomy can cure aldosterone excess and hypokalemia, but not necessarily hypertension. The prevalence of primary aldosteronism in the general population is not known. Its prevalence in referred hypertensive populations is estimated to be between 6 and 13%, of which 1.5 to 5% have an aldosterone-producing adenoma or primary unilateral adrenal hyperplasia. Taking into account referral biases, the prevalence of surgically correctable primary aldosteronism is probably less than 1.5% in the hypertensive population and less than 0.3% in the general adult population. Surgically correctable primary aldosteronism is sought in patients with hypokalemic, severe or resistant forms of hypertension. Recent recommendations suggest screening for primary aldosteronism using the aldosterone to renin ratio. Patients with a raised ratio then undergo confirmatory suppression tests. The differential diagnosis of hypokalemic hypertension with low renin includes mineralocorticoid excess, with the mineralocorticoid being cortisol or 11-deoxycorticosterone, apparent mineralocorticoid excess, pseudo-hypermineralocorticoidism in Liddle syndrome or exposure to glycyrrhizic acid. Once the diagnosis is confirmed, adrenal computed tomography is performed for all patients. If surgery is considered, taking into consideration the clinical context and the desire of the patient, adrenal vein sampling is performed to detect whether or not aldosterone hypersecretion is unilateral. Laparoscopic surgery for unilateral aldosterone hypersecretion is associated with a morbidity of about 8%, with most complications being minor. It generally results in the normalization of aldosterone secretion and kalemia, and in a large decrease in blood pressure, but normotension without treatment is only achieved in half of all cases. Normotension following adrenalectomy is more frequent in young patients with recent hypertension than in patients with long-standing hypertension or a family history of hypertension.

One-year effectiveness and safety of open-label losartan/hydrochlorothiazide combination therapy in Japanese patients with hypertension uncontrolled with ARBs or ACE inhibitors

The long-term antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been appropriately evaluated in Japan. In this study, treated hypertensive patients taking angiotensin-receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) regimens not at blood pressure (BP) goals proposed by the Japanese Society of Hypertension (JSH) were switched to losartan/HCTZ combinations and followed for 1 year. Data analysis included 244 patients aged 64.5+/-10.7 years, 56% male, 27% with diabetes mellitus and 36% with dyslipidemia. Pre-switching BP 157+/-16/88+/-10 mm Hg promptly decreased and maintained a steady state, reaching 132+/-15/77+/-9 mm Hg (P<0.001) 1 year later. After 1 year of treatment, 50% of patients cleared the goals of the JSH guideline for systolic BP and 79% for diastolic BP. Patients with maximal doses of ARBs tended to show larger decreases in BP (159+/-11/90+/-10 to 128+/-10/75+/-8 mm Hg, P<0.001, n=32). Clinical and laboratory adverse events were reported for 29 patients (11%), but serious abnormalities were not observed. In particular, plasma levels of uric acid (UA) were well-maintained for 1 year, and significant decreases in UA were observed in patients with higher levels of UA (>/=7.0 mg dl(-1)). Losartan/HCTZ combinations showed strong and steady hypotensive abilities and acceptable safety and tolerability in patients currently not at BP goals with regimens including ARBs or ACEIs in Japan.

Effects of Some .BETA.-Adrenoceptor Antagonists on Orthostatic Hypotension in Repeatedly Cold- (SART-) Stressed Rats

Rats stressed by specific alternation of rhythm in temperature (SART) show various symptoms of disautonomia, increased pulse rates, continuous hypotension, and severe orthostatic hypotension (OH) when they are subjected to postural change. The OH symptoms are improved by muscarinic M2-receptor blockers. In the present study, effects of beta-adrenoceptor blocking agents on OH in SART-stressed rats were investigated. Anesthetized rats were restrained on a board in the supine position, and direct blood pressure and ECG were measured automatically using Fluclet Jr.2. Postural change was performed by raising the rat's head up to a 60 degrees angle for 4 min. Unstressed rats treated with hexamethonium showed large decrease in blood pressure, small reflex from the bottom of pressure and decreased tachycardia reflex, whereas isoproterenol showed little changes. In SART-stressed rats, isoproterenol alleviated the decrease in blood pressure in postural change, brought large reflex from the bottom of pressure and increased tachycardia reflex, whereas hexamethonium had little changes. Propranolol and atenolol induced the similar changes as those seen by hexamethonium. ICI-118,551, a selective beta2-adrenoceptor antagonist showed large reflex from the bottom of pressure and increased tachycardia reflex in stressed rats, whereas little changes in unstressed rats. In conclusion, it was suggested that the hypotension in OH manifestation time of rats reflects the state of peripheral blood vessels, and beta1-adrenoceptors played a role in compensatory tachycardia reflex and beta2-adrenoceptors in blood pressure reflex. The circulatory regulation in SART-stressed rats seems to be poorly functioning in nervous reflex in postural changes.

Effects of thoracic blood volume on Valsalva maneuver.

The Valsalva maneuver (VM) is frequently used to test autonomic function. However, the VM is also affected by changes in blood volume and blood volume redistribution. We hypothesized that even a standardized VM may produce a wide range of thoracic blood volume shifts. Larger blood volume shifts in some normovolemic individuals may be sufficient to induce decreases in blood pressure (BP) that preclude autonomic restoration of BP in phase II of the VM. To test this hypothesis, we studied 17 healthy volunteers aged 15-22 yr. All had similar vasoconstrictor responses when supine and upright and normal blood volume measurements. We assessed changes in thoracic blood volume by impedance plethysmography before and during the VM performed while subjects were supine. In some subjects, large decreases in BP were produced by thoracic hypovolemia. The maximum fractional decrease in BP correlated well (r(2) = 0.64; P < 0.001) with thoracic hypovolemia and with systolic BP at the end of phase II of the VM (r(2) = 0.67; P < 0.001). The BP overshoot in phase IV of the VM was uncorrelated to phase II changes, which suggests intact autonomic vasoconstriction. We conclude that the BP decrease during the VM is related to a variable decrease in thoracic blood volume that may be sufficient to preclude pressure recovery during phase II even with normal resting peripheral vasoconstriction. The VM depends on vascular as well as autonomic activation, which broadens its utility but complicates its analysis.

Dietary sodium and blood pressure.

The importance of dietary sodium chloride in the regulation of blood pressure has received much attention over the past few years. This area of research and knowledge has been controversial for several reasons. The major reason for controversy is that the science of the relationship is difficult to ascertain. Population science is limited by the narrow range of dietary sodium intake by most populations and individuals and the multiple confounders in those populations at the extremes of intake. Results from clinical trials have been difficult to interpret because of the difficulty in maintaining a given level of sodium intake over a period of time sufficient for study. Furthermore, basic science studies have been challenged by identifying appropriate models that mimic salt-sensitive hypertension in humans. Moreover, a lack of a well-funded proponent in industry complicates the research challenges. Guyton’s concept that the role of the kidney in handling sodium is key to the long-term regulation of blood pressure is now generally accepted.1 However, the exact role that dietary sodium plays in this relationship remains controversial. The relationship between renal handling of sodium and blood pressure is apparently influenced by a complex combination of factors including nutritional, other environmental, genetic, neurohormonal, and metabolic factors. The skepticism of many regarding the role of dietary sodium in blood pressure regulation and control has been tempered by the results of the DASH sodium study.2 Most acknowledge that this study reliably confirmed the benefit of dietary sodium restriction in blood pressure management. The study showed a dose-dependent impact of dietary sodium restriction on blood pressure in older hypertensive and nonhypertensive subjects. For many interested in this area of research, the questions have shifted as a result of the DASH sodium study. Rather than questioning whether dietary sodium is important, many investigators have turned their …