Differences In Blood Pressure Responses Research Articles

Sex Differences in Blood Pressure Response to Dietary Salt in Aged Rats

Background: The impact of dietary salt intake on blood pressure (BP) and its variability is critical for understanding cardiovascular risks, yet there is a scarcity of data exploring these effects across different sexes, particularly in the context of aging. Methods: This study examined the effects of varying salt diets on BP among aged female and male Sprague-Dawley rats (22-24 months). Subjects were administered either a control (0.4% NaCl), low (0.1% NaCl), or moderate-high (1% NaCl) salt diet for 12 weeks. BP levels and variability were measured at baseline, 2, 4, 8, and 12 weeks after dietary onset. Results: Preliminary findings revealed that, from the eighth week following dietary initiation, aged male rats exhibited a pronounced elevation in systolic BP when exposed to all types of diets, in contrast to aged female rats consuming low-salt diets. Additionally, aged male rats presented with a marked rise in diastolic BP upon consumption of both control and high-salt diets relative to female rats across all diets from the eighth week onward. Although systolic BP variability did not differ significantly between sexes, there were marked sex-specific differences in diastolic BP variability. Conclusions: The study identified sex-specific responses in BP and its variability to dietary salt intake in aged rats, with male rats showing heightened sensitivity. These findings underscore the importance of considering sex as a biological variable in dietary and cardiovascular health research. This research was funded by the START-UP FUNDING OF HANGZHOU NORMAL UNIVERSITY, grant number 4255C50221204123 (Dr. Fen Sun). 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.

Predictors of blood pressure response to continuous positive airway pressure treatment in patients with sleep apnea.

Sleep apnea is associated with hypertension. Metaanalyses indicate that treatment of sleep apnea by continuous positive airway pressure (CPAP) reduces blood pressure (BP) by a mean of 3 mmHg. To date, predictors of BP response to CPAP remain incompletely understood. We hypothesized that the magnitude of CPAP-induced BP reduction depends on baseline apnea-hypopnea index (AHI) and the extent of daytime sleepiness. We performed a retrospective study on the association of BP response to CPAP with polysomnographic readings, intensity of sleepiness (measured by Epworth Sleepiness Scale, ESS), and epidemiologic parameters in 2461 patients with obstructive sleep apnea. BP response was defined as the difference between office BP at polysomonography examinations before and after initiation of CPAP. Five hundred and fifty-five patients fulfilled all inclusion and exclusion criteria and were included in the analysis. Median monthly CPAP usage was 143.7 h (85.4-204.1 h). BP was significantly higher at baseline than at follow-up (129.9 ± 15.5 vs. 128.3 ± 15.2, P = 0.021) resulting in mean reduction of BP of -1.5 ± 19.2 mmHg. patients with a higher than median baseline AHI (median 21) showed a more pronounced reduction of BP than those with lower AHI (AHI ≥21: 130.5 ± 15.3 vs. 128.6 ± 14.6, P = 0.06; AHI <21: 129.5 ± 15.8 vs. 127.9 ± 15.8, P = 0.18). CPAP therapy led to a significant reduction in sleepiness (8.3 ± 4.8 vs. 6.6 ± 4.5, P < 0.0001). Those subjects with higher than median sleepiness score (ESS ≥8), however, did not show a significant difference in BP response compared with those with a lower sleepiness score. Receiver-operating characteristic (ROC) curve analyses investigating the accuracy of AHI and ESS to predict a BP reduction at least 5 mmHg revealed an AUC of 0.51 and 0.52, respectively. The study confirms that CPAP therapy for sleep apnea has a mild BP lowering effect. Although this effect is slightly higher in patients with above-average AHI, neither AHI nor ESS can be used to define threshold values predicting a BP decrease at least 5 mmHg.

Progression of obstructive sleep apnoea after renal denervation is not associated with hypertension exaggeration

PurposeIn a cohort, observational prospective trial, we assessed the long-term dynamics of sleep-disordered breathing in patients with resistant hypertension after renal denervation and their association with blood pressure change at remote follow-up.Materials and methodsTwenty-eight patients with stable hypertension who were recruited for endovascular radiofrequency renal denervation in 2012–2019 and had valid both baseline and follow-up sleep study, were included in the analysis. All patients underwent physical examination, anthropometry, office and ambulatory blood pressure measurements, blood and urine tests, kidney visualization, and full polysomnography before and within 12–36 months after renal denervation.ResultsThe average follow-up comprised 30.1 ± 8.4 months. At long-term follow-up, no significant changes in creatinine level, estimated glomerular filtration rate, body mass index were registered. There was a significant increase in sleep apnea severity indices: the mean change in apnea-hypopnea index comprised 9.0(-21.1;25.2) episodes/h, in oxygen desaturation index 6.5(-16.8;35.9) episodes/h, in the average SpO2 -1.7(-5.6;1.9)%. Over 12-month follow-up, there were no significant differences in blood pressure response in patients with and without sleep apnea. The baseline apnea-hypopnea and oxygen desaturation indices and the mean SpO2 were associated with the circadian blood pressure profile at follow-up, but did not correlate with the blood pressure response.ConclusionsAlthough the severity of sleep apnea worsens at > 12 months follow-up after renal denervation, this is not associated with hypertension exaggeration.

Adjusting for muscle strength and body size attenuates sex differences in the exercise pressor reflex in young adults.

Females typically exhibit lower blood pressure (BP) during exercise than males. However, recent findings indicate that adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI; metaboreflex isolation). In addition, body size is associated with HG strength but its contribution to sex differences in exercising BP is less appreciated. Therefore, the purpose of this study was to determine whether adjusting for strength and body size would attenuate sex differences in BP during HG and PEI. We obtained beat-to-beat BP in 110 participants (36 females, 74 males) who completed 2 min of isometric HG exercise at 40% of their maximal voluntary contraction followed by 3 min of PEI. In a subset (11 females, 17 males), we collected muscle sympathetic nerve activity (MSNA). Statistical analyses included independent t tests and mixed models (sex × time) with covariate adjustment for 40% HG force, height2, and body surface area. Females exhibited a lower absolute 40% HG force than male participants (Ps < 0.001). Females exhibited lower Δsystolic, Δdiastolic, and Δmean BPs during HG and PEI than males (e.g., PEI, Δsystolic BP, 15 ± 11 vs. 23 ± 14 mmHg; P = 0.004). After covariate adjustment, sex differences in BP responses were attenuated. There were no sex differences in MSNA. In a smaller strength-matched cohort, there was no sex × time interactions for BP responses (e.g., PEI systolic BP, P = 0.539; diastolic BP, P = 0.758). Our data indicate that sex differences in exercising BP responses are attenuated after adjusting for muscle strength and body size.NEW & NOTEWORTHY When compared with young males, females typically exhibit lower blood pressure (BP) during exercise. Adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI), but the contribution of body size is unknown. Novel findings include adjustments for muscle strength and body size attenuate sex differences in BP reactivity during exercise and PEI, and sex differences in body size contribute to HG strength differences.

Cardiovascular responses to combined mechanoreflex and metaboreflex activation in healthy adults: effects of sex and low- versus high-hormone phases in females.

Females generally have smaller blood pressure (BP) responses to isolated muscle mechanoreflex and metaboreflex activation compared with males, which may explain sex differences in BP responses to voluntary exercise. The mechanoreflex may be sensitized during exercise, but whether mechanoreflex-metaboreflex interactions differ by sex or variations in sex hormones remains unknown. Thirty-one young healthy subjects (females, n = 16) performed unilateral passive cycling (mechanoreflex), active cycling (40% peak Watts), postexercise circulatory occlusion (PECO; metaboreflex), and passive cycling combined with PECO (combined mechanoreflex and metaboreflex activation). Beat-to-beat BP, heart rate, inactive leg vascular conductance, and active leg muscle oxygenation were measured. Ten females underwent exploratory testing during low- and high-hormone phases of their self-reported menstrual cycle or oral contraceptive use. Systolic BP and heart rate responses did not differ between sexes during active cycling [Δ30 ± 9 vs. 29 ± 11 mmHg (males vs. females), P = 0.9; Δ33 ± 8 vs. 35 ± 6 beats/min, P = 0.4] or passive cycling with PECO (Δ26 ± 11 vs. 21 ± 10 mmHg, P = 0.3; Δ14 ± 7 vs. 18 ± 15 beats/min, P = 0.3). Passive cycling with PECO revealed additive, not synergistic, effects for systolic BP [males: Δ23 ± 14 vs. 26 ± 11 mmHg (sum of isolated passive cycling and PECO vs. combined activation); females: Δ26 ± 11 vs. 21 ± 12 mmHg, interaction P = 0.05]. Results were consistent in subset analyses with sex differences in active cycling BP (P > 0.1) and exploratory analyses of hormone phase (P > 0.4). Despite a lack of statistical equivalence, no differences in cardiovascular responses were found during combined mechanoreflex-metaboreflex activation between sexes or hormone levels. These results provide preliminary data regarding the involvement of muscle mechanoreflex-metaboreflex interactions in mediating sex differences in voluntary exercise BP responses.NEW & NOTEWORTHY The muscle mechanoreflex may be sensitized by metabolites during exercise. We show that cardiovascular responses to combined mechanoreflex (passive cycling) and metaboreflex (postexercise circulatory occlusion) activation are primarily additive and do not differ between males and females, or across variations in sex hormones in females. Our findings provide new insight into the contributions of muscle mechanoreflex-metaboreflex interactions as a cause for prior reports that females have smaller blood pressure responses to voluntary exercise.

Acute nitric oxide synthase inhibition induces greater increases in blood pressure in female versus male Wistar Kyoto rats.

Nitric oxide (NO) contributes to blood pressure (BP) regulation via its vasodilatory and anti-inflammatory properties. We and others previously reported sex differences in BP in normotensive and hypertensive rat models where females have lower BP than age-matched males. As females are known to have greater NO bioavailability than age-matched males, the current study was designed to test the hypothesis that anesthetized female normotensive Wistar Kyoto rats (WKY) are more responsive to acute NOS inhibition-induced increases in BP compared to male WKY. Twelve-week-old male and female WKY were randomized to infusion of the nonspecific NOS inhibitor NG -nitro-L-arginine methyl ester (L-NAME, 1 mg/kg/min) or selective NOS1 inhibition with vinyl-L-NIO (VNIO, 0.5 mg/kg/min) for 60 min. Mean arterial BP, glomerular filtration rate (GFR), urine volume, and electrolyte excretion were assessed before, and during L-NAME or VNIO infusion. L-NAME and VNIO significantly increased BP in both sexes; however, the increase in BP with L-NAME infusion was greater in females versus males compared to baseline BP values. Acute infusion of neither L-NAME nor VNIO for 60 min altered GFR in either sex. However, urine volume, sodium, chloride and potassium excretion levels increased comparably in male and female WKY with L-NAME and VNIO infusion. Our findings suggest sex differences in BP responses to acute non-isoform-specific NOS inhibition in WKY, with females being more responsive to L-NAME-induced elevations in BP relative to male WKY. However, sex differences in the BP response did not coincide with sex differences in renal hemodynamic responses to acute NOS inhibition.

Gender-specific effect of outdoor temperature and seasonal variation on blood pressure components: a cross-sectional study on Iranian adults from 2015 to 2018.

Blood pressure (BP) is influenced by both individual and environmental factors such as ambient temperature. However, the gender-stratified and component-specific impact of temperature on BP is not well understood. Herein, we examined the temperature and seasonal effects on four main BP components, namely systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), in both genders. A total of 8990 (3954 men) Tehranian adults during 2015-2018 were included. Linear regression models for analyzing data in three models including unadjusted, age-adjusted, and further adjusted for known sociodemographic and cardiovascular confounders were conducted. Among women, each 10°C increment was associated with a significant decrease of - 0.48mmHg (95% confidence interval (CI): - 0.86, - 0.19) and - 0.65mmHg (- 0.76, - 0.41) in SBP and MAP, respectively. In men, the corresponding value for SBP was - 0.46 (- 0.82, - 0.16) mmHg (P = 0.058). Gender-specific analysis in each season showed that among women, PP increased in autumn and winter with each 10°C decrease (P < 0.05). The mean increase in SBP (3.4 and 2.06mmHg in women and men, respectively), DBP (1.66 and 1.19mmHg), and MAP (2.71 and 1.12mmHg) was observed during winter compared to summer (all P < 0.05). PP showed seasonality only in women (1.46mmHg, P-value = 0.003). In both genders, SBP in age > 60years was more susceptible to variation compared to younger ages. Furthermore, obese women had more SBP changes compared to their non-obese counterparts (all P for interaction < 0.05). In conclusion, there was a sex difference in BP response to the outdoor temperature, with higher vulnerability among women. The reverse relation between temperature and BP occurred particularly among elderly and obese individuals. Careful monitoring of BP in cold seasons, specifically in the mentioned subgroups, could potentially attenuate cardiovascular risks.

Adjusting For Exercise Intensity Attenuates Sex Differences In Blood Pressure During Exercise In Healthy Adults

PURPOSE: The exercise pressor reflex, composed of the muscle mechano- and metaboreflex, increases blood pressure (BP). Compared to males, healthy female adults typically exhibit blunted BP responses to exercise. However, recent work suggests that sex differences in BP during isometric handgrip (HG) exercise and post-exercise ischemia (PEI; metaboreflex isolation) are attenuated after adjusting for differences in maximal voluntary contraction (MVC). Therefore, the purpose of this study was to determine whether sex differences in BP responses during HG and PEI would be attenuated after adjustment for submaximal HG squeezing force. METHODS: We analyzed data from 95 participants including 34 females (age: 24±4 years, BMI: 24±4 kg/m2, screening BP: 106±13/64±9 mmHg, Mean ± SD) and 61 males (age: 25±5 years, BMI: 2±3 kg/m2, screening BP: 113±11/66±9 mmHg). All females were tested during days 1-5 of their menstrual cycle. Maximal HG force for each participant was defined as the average of three MVCs. Following a 10-minute baseline period, participants performed static static HG exercise at 40% of their average MVC for two minutes followed by three minutes of PEI via brachial occlusion. We obtained beat-to-beat BP readings via finger photoplethysmography (Finometer). Statistical analyses included t-tests, 2-way ANOVAs (sex x time), and ANCOVAs (average HG force as a covariate). RESULTS: Females exhibited a lower absolute 40% HG force than males (105±30 N v. 169±45 N, p<0.001). There was a significant sex x time interaction for ∆ systolic BP during HG (e.g., minute 2, females: 20±12 mmHg v. 28±18 mmHg in males, p=0.014), but not ∆ diastolic (p=0.106) or ∆ mean BP (p=0.058). After adjusting for absolute HG force, the sex difference for peak ∆ systolic BP during HG was attenuated (p=0.072). During PEI there were sex x time interactions for ∆ systolic, ∆ diastolic, and ∆ mean BP (p<0.05 for all) and adjustment for HG force did not attenuate these differences. Additionally, in a small strength-matched cohort (N=48, 29 females, female HG force mean = 107±23 N, male HG force mean = 118 ± 24 N, p=0.092) there was not a significant sex difference for peak ∆ systolic BP during HG (p=0.667) or PEI (p=0.828). CONCLUSIONS: Our data indicate that the sex difference in BP reactivity is attenuated after adjusting for absolute HG force during exercise.

Genetic Contributors of Efficacy and Adverse Metabolic Effects of Chlorthalidone in African Americans from the Genetics of Hypertension Associated Treatments (GenHAT) Study.

Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies have shown considerable interpersonal differences in BP response to antihypertensive treatment, suggesting a genetic component. Utilizing data from 4297 AA participants randomized to chlorthalidone from the Genetics of Hypertension Associated Treatments (GenHAT) study, we aimed to identify variants associated with the efficacy of chlorthalidone. An additional aim was to find variants that contributed to changes in fasting glucose (FG) in these individuals. We performed genome-wide association analyses on the change of systolic and diastolic BP (SBP and DBP) over six months and FG levels over 24 months of treatment. We sought replication in the International Consortia of Pharmacogenomics Studies. We identified eight variants statistically associated with BP response and nine variants associated with FG response. One suggestive LINC02211-CDH9 intergenic variant was marginally replicated with the same direction of effect. Given the impact of hypertension in AAs, this study implies that understanding the genetic background for BP control and glucose changes during chlorthalidone treatment may help prevent adverse cardiovascular events in this population.

Sex difference in blood pressure response to orthostatic stress: effects of transcutaneous electrical nerve stimulation.

We investigated sex differences in blood pressure (BP) response to transcutaneous electrical nerve stimulation (TENS) during orthostatic stress (ORT). Seventeen healthy young adults (males = 9; females = 8) underwent TENS or SHAM stimulus applied in the cervicothoracic region for 30 min in the supine position followed by 10 min in the orthostatic position. Electrocardiogram and BP were continuously recorded at rest and during ORT. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were calculated from the BP signal. Orthostatic challenge decreased BP similarly for both sexes during ORT, a deeper drop in CO and a slight increase in heart rate were found in women compared with men ( P = 0.03 and 0.05, respectively). TENS evoked a pronounced fall in SBP in men compared with the SHAM condition ( P < 0.05). TENS has no effect on SBP in women compared with the SHAM condition. This finding suggests a possible modulatory effect by one cervicothoracic TENS session on sympathetic tonus in healthy men.

Acute cardiac autonomic and haemodynamic responses to leg and arm isometric exercise.

Acute cardiovascular responses following a single session of isometric exercise (IE) have been shown to predict chronic adaptations in blood pressure (BP) regulation. It was hypothesised that exercises which recruit more muscle mass induce greater reductions in BP compared to exercises using smaller muscle mass. To test this hypothesis, the current study aimed to compare the acute haemodynamic and autonomic responses to a single session of isometric wall squat (IWS) and isometric handgrip (IHG) training. Twenty-six sedentary participants performed a single IWS and IHG session in a randomised cross-over design, with training composed of 4 × 2-min contractions, with 2-min rest, at 95 HRpeak and 30% MVC respectively. Haemodynamic and cardiac autonomic variables were recorded pre, during, immediately post, and 1-h post-exercise, with the change from baseline for each variable used for comparative analysis. During IWS exercise, there was a significantly greater increase in systolic BP (P < 0.001), diastolic BP (P < 0.001), mean BP (P < 0.001), heart rate (P < 0.001), and cardiac output (P < 0.001), and a contrasting decrease in baroreflex effectiveness index (BEI) and cardiac baroreceptor sensitivity (cBRS). In the 10-min recovery period following IWS exercise, there was a significantly greater reduction in systolic BP (P = 0.005), diastolic BP (P = 0.006), mean BP (P = 0.003), total peripheral resistance (TPR) (P < 0.001), BEI (P = 0.003), and power spectral density (PSD-RRI) (P < 0.001). There were no differences in any variables between conditions 1-h post exercise. Isometric wall squat exercise involving larger muscle mass is associated with a significantly greater post-exercise hypotensive response during a 10-min recovery window compared to smaller muscle mass IHG exercise. The significantly greater reduction in TPR may be an important mechanism for the differences in BP response.

Differential Effects of Cardiac Rehabilitation in Obese and Non-Obese Population.

BackgroundCardiac rehabilitation (CR) improves outcomes in patients with heart disease. We investigated the differences in outcomes of comprehensive phase II CR in obese and non-obese patients.MethodsWe performed a retrospective analysis of functional outcomes including metabolic equivalents (METS), heart rate (chronotropic competence - CC), and blood pressure response (BPR) in 178 patients undergoing CR based on underlying body mass index (BMI). Demographic and clinical variables were assessed for age, gender, race, smoking, hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, stroke, heart failure, medication use, and several sessions attended.ResultsInitial CC and METS were impaired in majority of patients attending CR, whereas BPR to exercise was mostly preserved. Significant improvement occurred in CC (non-obese: 0.71 ± 0.11 vs 0.76 ± 0.11, p < 0.001; obese: 0.72 ± 0.10 vs 0.75 ± 0.12, p = 0.0010) and METS (non-obese: 4.96 ± 1.98 vs 7.33 ± 2.94, p < 0.001; obese: 4.39 ± 1.81 vs 6.79 ± 3.34, p < 0.001). Post-CR obese patients were able to reach similar level of physical activity as non-obese patients (6.79 ± 3.34 vs 7.33 ± 2.94; p = 0.2). Improvement in BPR was only seen in non-obese patients (24.02 ± 20.07 vs 30.18 ± 21.93; p = 0.019). Improvement in functional variables occurred despite increase in BMI in non-obese (25.91 ± 2.85 vs 26.21 ± 2.96; p = 0.031), and there was no significant change in BMI in obese (35.30 ± 5.60 vs 34.93 ± 5.42; p > 0.05).ConclusionCR concurrently improves functional outcomes in both obese and non-obese patients despite no associated weight loss. The difference in BPR, however, is seen in only non-obese individuals. Future studies are needed to validate the role of weight-optimized CR protocols as a potential target for improving cardiac outcomes.

Muscle Oxygenation, Neural, and Cardiovascular Responses to Isometric and Workload-matched Dynamic Resistance Exercise.

Differences in blood flow patterns and energy cost between isometric and dynamic resistance exercise may result to variant cardiovascular, neural, and muscle metabolic responses. We aimed to compare the cardiovascular, baroreceptor sensitivity, and muscle oxygenation responses between workload-matched, large muscle-mass isometric and dynamic resistance exercises. Twenty-four young men performed an isometric and a dynamic double leg-press protocol (4 sets×2 min) with similar tension time index (workload). Beat-by-beat hemodynamics, baroreceptor sensitivity, muscle oxygenation, and blood lactate were assessed. The increase in blood pressure was greater (p<0.05) in the 1st set during dynamic than isometric exercise (by ~4.5 mmHg), not different in the 2nd and 3rd sets, and greater in the 4th set during isometric exercise (by ~5 mmHg). Dynamic resistance exercise evoked a greater increase in heart rate, stroke volume, cardiac output, and contractility index (p<0.05), and a greater decline in peripheral resistance, baroreceptor sensitivity, and cardiac function indices than isometric exercise (p<0.05). Participants exhibited a greater reduction in muscle oxyhemoglobin and a greater increase in muscle deoxyhemoglobin in dynamic versus isometric exercise (p<0.001-0.05), with no differences in total hemoglobin and blood lactate. In conclusion, large muscle-mass, multiple-set isometric exercise elicits a relatively similar blood pressure but blunted cardiovascular and baroreceptor sensitivity responses compared to workload-matched dynamic resistance exercise. Differences in blood pressure responses between protocols appear small (~5 mmHg) and are affected by the number of sets. The muscle oxidative stimulus is greater during dynamic resistance exercise than workload-matched isometric exercise.

Sex Differences in Muscle Metaboreflex Activation after Static Handgrip Exercise.

Larger blood pressure (BP) responses to relative-intensity static exercise in men versus women are thought to involve altered muscle metaboreflex activation, but whether this is because of an intrinsic sex difference in metabolite production or differences in muscle strength and absolute load is unknown. Continuous BP and heart rate were recorded in 200 healthy young men and women (women: n = 109) during 2 min of static handgrip exercise at 30% of maximal voluntary contraction (MVC), followed by 2 min of postexercise circulatory occlusion (PECO). Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (n = 39; women, n = 21), permitting calculation of signal-averaged resting sympathetic transduction (MSNA-diastolic BP). Sex differences were examined with and without statistical adjustment for MVC. Multivariate regression analyses were performed to identify predictors of BP responses. Men had larger systolic BP responses (interactions, P < 0.0001) to static handgrip exercise (24 ± 10 vs 17 ± 9 mm Hg [mean ± SD], P < 0.0001) and PECO (20 ± 11 vs 16 ± 9 mm Hg, P < 0.0001). Adjustment for MVC abolished these sex differences in BP (interactions, P > 0.7). In the subset with MSNA, neither burst frequency or incidence responses to static handgrip exercise or PECO differed between men and women (interactions, P > 0.2). Resting sympathetic transduction was also similar (P = 0.8). Multiple linear regression analysis showed that MVC or the change in MSNA, were predictors of BP responses to static handgrip, but only MVC was associated with BP responses during PECO. Sex differences in absolute contraction load contribute to differences in BP responses during muscle metaboreflex isolation using PECO. These data do not support an intrinsic effect of sex as being responsible for exercise BP differences between men and women.

Sex-specific differences in blood pressure responses following acute high-altitude exposure.

Sex-specific differences in blood pressure responses following acute high-altitude exposure.

Age and sex differences in blood pressure responses during hyperpnoea.

What is the central question of this study? Increased respiratory muscle activation is associated with neural and cardiovascular consequences via the respiratory muscle-induced metaboreflex. Does ageing and/or sex influence the arterial blood pressure response during voluntary normocapnic incremental hyperpnoea? What is the main finding and its importance? The increase in blood pressure during hyperpnoea was smaller in younger females than in older females, whereas no difference was found between older males and older females. The blunted respiratory muscle-induced metaboreflex in younger females is normalized with advancing age, whereas ageing has no such effect in males. We hypothesized that older females (OF) have a greater arterial blood pressure response to increased respiratory muscle work compared with younger females (YF) and that no such difference exists between older males (OM) and younger males (YM). To test these hypotheses, cardiovascular responses during voluntary normocapnic incremental hyperpnoea were evaluated and compared between older and younger subjects. An incremental respiratory endurance test (IRET) was performed as follows: target minute ventilation was initially set at 30% of the maximal voluntary ventilation (MVV12) and was increased by 10% of MVV12 every 3min. The test was terminated when the subject could not maintain the target percentage of MVV12. Heart rate and mean arterial blood pressure (MAP) were recorded continuously. The increase in MAP from baseline (ΔMAP) during the IRET in OM (+24.0±14.7mmHg, mean ± SD) did not differ (P=0.144) from that in YM (+24.3±13.4mmHg), but it was greater (P=0.004) in OF (+31.2±11.6mmHg) than in YF (+10.3±5.5mmHg). No significant difference in ΔMAP during the IRET was observed between OM and OF (P=0.975). These results suggest that the respiratory muscle-induced metaboreflex is blunted in YF, but it could be normalized with advancing age. In males, ageing has little effect on the respiratory muscle-induced metaboreflex. These results show no sex difference in the respiratory muscle-induced metaboreflex in older adults.

Abstract 16461: Are Inducible Exercise Left Ventricular Outflow Tract Gradients Associated With Adverse Outcomes in Pediatric Hypertrophic Cardiomyopathy?

Introduction: Adverse outcomes in hypertrophic cardiomyopathy (HCM) includes arrhythmias, myocardial fibrosis, heart failure, and sudden cardiac arrest (SCA). These are well documented in children. Exercise stress echocardiography (ESE) can identify the severity and mechanism of left ventricular outflow tract (LVOT) obstruction that may not be present at rest. Our aim was to compare clinical outcomes in pediatric patients with varying severity of LVOT obstruction. Methods: We reviewed records of patients &lt; 22 years with HCM who underwent staged ESE Jan 2009 - Dec 2019 at our center. Patients were divided into 3 groups: no resting or exercise LVOT gradient (Group 1), no resting gradient with LVOT gradient &gt; 30 mmHg at peak exercise (Group 2), and resting LVOT gradient &gt; 30 mmHg (Group 3). We assessed echocardiographic indices, advanced imaging, and clinical data. Statistical analysis performed with p-value &lt;0.05. Results: 93 patients met inclusion criteria. 6 SCA events occurred, though not during ESE.. Patients in Group 3 were classified less often as NYHA Class 1 compared to Group 1 or Group 2, (p &lt; 0.01). Group 3 had the highest rate of myectomy (p=0.005) and ICD placement (p=0.003). There was no significant difference in exercise symptoms, peak oxygen consumption, or ischemic changes during ESE between the groups. Peak heart rate was also higher in Group 2 with no difference in blood pressure response. Groups were not associated with family history of disease, positive gene status, SCA, or the presence of fibrosis (Table). LVOT gradients differed as early as Stage 1 in Groups 1 &amp; 2. Inducible LVOT obstruction was most commonly midcavitary in Group 2. Conclusion: The presence of resting versus inducible LVOT obstruction in pediatric HCM does not appear associated with adverse outcomes. This may be hampered by the rarity of events in pediatrics. The predominant mechanism of inducible LVOT obstruction was midcavitary, which has a link to adverse long-term outcomes in adult HCM.

Impact of Mineralocorticoid Receptor and Angiotensin II Type 1 Receptor Antagonism on Blood Pressure Regulation in Obese Zucker Rats: Role of Sex Differences.

Previous studies suggest that obesity-induced hypertension in females, but not males, is due to leptin-mediated stimulation of aldosterone secretion and subsequent activation of the mineralocorticoid receptor (MR). Although angiotensin II type 1 receptor (AT1R) antagonism lowers blood pressure (BP) in male obese Zucker rats (OZR), which have defective leptin signaling, the potential role of sex differences in BP responses to renin-angiotensin-aldosterone system blockade, including MR antagonism, in obesity is still unclear. We tested the cardiovascular effects of MR antagonism, alone or in combination with AT1R blockade in male and female OZR (n = 5/sex) and lean Zucker rats (n = 7/sex). BP and heart rate (HR) were measured by telemetry 24 hour/day. After a 6-day control period, spironolactone (40 mg/kg/day) was given for 10 days followed by a 7-day combined treatment with losartan (20 mg/kg/day), and followed by 6-day post-treatment recovery period. Compared with lean rats, OZR were hypertensive (mean arterial pressure: 115 ± 4 vs. 104 ± 2 and 111 ± 1 vs. 100 ± 3 mm Hg for males and females) and had lower HR (355 ± 9 vs. 393 ± 7 and 367 ± 10 vs. 412 ± 13 bpm). MR blockade alone did not alter BP or HR in lean or obese male and female Zucker rats, whereas combined treatment reduced BP in obese and lean rats by 31 ± 3 vs. 21 ± 1 and 8 ± 1 vs. 5 ± 1 mm Hg in males and females, respectively. No changes were observed in HR. These results suggest that there are important sex differences in BP responses to chronic AT1R blockade but no major involvement of MR activation in BP regulation in OZR.

Adrenergic Autoantibody-Induced Postural Tachycardia Syndrome in Rabbits.

BackgroundPrevious studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. The objective of this study was to examine the impact of these autoantibodies on cardiovascular responses to postural changes and adrenergic orthosteric ligand infusions in immunized rabbits.Methods and ResultsEight New Zealand white rabbits were coimmunized with peptides from the α1‐adrenergic receptor and β1‐adrenergic receptor (β1AR). Tilt test and separate adrenergic agonist infusion studies were performed on conscious animals before and after immunization and subsequent treatment with epitope‐mimetic peptide inhibitors. At 6 weeks after immunization, there was a greater percent increase in heart rate upon tilting compared with preimmune baseline. No significant difference in blood pressure response to tilting was observed. The heart rate response to infusion of the β‐adrenoceptor agonist isoproterenol was significantly enhanced in immunized animals, suggesting a positive allosteric effect of β1AR antibodies. In contrast, the blood pressure response to infusion of the α1‐adrenergic receptor agonist phenylephrine was attenuated in immunized animals, indicating a negative allosteric effect of α1‐adrenergic receptor antibodies. Injections of antibody‐neutralizing peptides suppressed the postural tachycardia and reversed the altered heart rate and blood pressure responses to orthosteric ligand infusions in immunized animals at 6 and 30 weeks. Antibody production and suppression were confirmed with in vitro bioassays.ConclusionsThe differential allosteric effect of α1‐adrenergic receptor and β1AR autoantibodies would lead to a hyperadrenergic state and overstimulation of cardiac β1AR. These data support evidence for an autoimmune basis for postural tachycardia syndrome.

SALT-SENSITIVE BLOOD PRESSURE RISE IN TYPE 1 DIABETES IS ACCOMPANIED BY INCAPACITY FOR VASODILATION – A RANDOMIZED EXPERIMENTAL CROSS-OVER STUDY

Objective: Diabetes mellitus type 1 (DM1) is suggested to be associated with salt sensitivity. However, strong evidence to support this is scarce, and the pathophysiology is not known. For a long time, the volume-regulating function of the kidney was thought to be the only important factor in salt-sensitive hypertension. Due to insufficient sodium excretion by the kidney, sodium excess was considered to increase extracellular fluid volume (ECFV) and cardiac output (CO), resulting in a blood pressure (BP) rise. However, recent publications put forward that systemic vascular resistance (SVR) might be central in BP regulation. We hypothesized that in salt-sensitive hypertension in DM1, vasodysfunction rather than increases in ECFV and CO plays a role.Design and method: We included 8 DM1 patients and 12 age-matched healthy controls (HC), with normal BP, body mass index, and kidney function. All subjects adhered to an 8-day low salt diet (LSD) and an 8-day high salt diet (HSD), in randomized order. After each diet, hemodynamic measurements included BP (Omron) and CO (Nexfin™), and SVR was calculated accordingly. To assess volume-dependent changes, ECFV, interstitial fluid volume (IFV) and plasma volume (PV) were calculated by the use of iohexol and 125I-albumin distribution. HC were divided in two subgroups: those with versus those without a BP increase after HSD. Results: After HSD, patients with DM1 showed a BP increase (mean arterial pressure HSD vs LSD (85 (5) mmHg vs. 80 (3) mmHg; P = 0.03) while BP in HC did not rise (78 (5) mmHg vs. 78 (5) mmHg; P = 0.85). The difference in BP response was not accompanied by differences in urinary sodium excretion between the DM1 patients and HC (Figure 1) nor by differences in CO, ECFV or ICF (Table 1). HC without a BP increase after HSD (n = 5) showed a SVR reduction after HSD, while this reduction was not present in the HC with a BP increase after HSD (n = 7) or in the DM1 patients (Figure 2, Table 1). Conclusions: DM1 is associated with increased salt sensitivity compared to HC, coinciding with incapacity for vasodilation.