Evening but not morning aerobic training improves sympathetic activity and baroreflex sensitivity in elderly patients with treated hypertension.

The blood pressure-lowering effect of aerobic training is preceded by improving cardiovascular autonomic control. We previously demonstrated that aerobic training conducted in the evening (ET) induces a greater decrease in blood pressure than morning training (MT). To study whether the greater blood pressure decrease after ET occurs through better cardiovascular autonomic regulation, this study aimed to compare MT versus ET on muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) in treated patients with hypertension. Elderly patients treated for hypertension were randomly allocated into MT (n = 12, 07.00-10.00 h) or ET (n = 11, 17.00-20.00 h) groups. Both groups trained for 10 weeks, 3 times/week, cycling for 45 min at moderate intensity. Beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and MSNA (microneurography) were assessed at the initial and final phases of the study at baseline and during sequential bolus infusions of sodium nitroprusside and phenylephrine (modified-Oxford technique) to evaluate cardiac and sympathetic BRS. Mean blood pressure decreased significantly after ET but not after MT (-9 ± 11 vs. -1 ± 8 mmHg, P = 0.042). MSNA decreased significantly only after ET with no change after MT (-12 ± 5 vs. -3 ± 7 bursts/100 heart beats, P = 0.013). Sympathetic BRS improved after ET but not after MT (-0.8 ± 0.7 vs. 0.0 ± 0.8 bursts/100 heart beats/mmHg, P = 0.052). Cardiac BRS improved similarly in both groups (ET: +1.7 ± 1.8 vs. MT: +1.4 ± 1.9 ms/mmHg, Pphase  ≤ 0.001). In elderly patients treated for hypertension, only ET decreased mean blood pressure and MSNA and improved sympathetic BRS. These findings revealed that the sympathetic nervous system has a key role in ET's superiority to MT in blood pressure-lowering effect. KEY POINTS: Reducing muscle nerve sympathetic activity and increasing sympathetic baroreflex sensitivity plays a key role in promoting the greater blood pressure reduction observed with evening training. These findings indicated that simply changing the timing of exercise training may offer additional benefits beyond antihypertensive medications, such as protection against sympathetic overdrive and loss of baroreflex sensitivity, independent markers of mortality. Our new findings also suggest new avenues of investigation, such as the possibility that evening aerobic training may be beneficial in other clinical conditions with sympathetic overdrive, such as congestive heart failure and hypertrophic cardiomyopathy.

Acute kidney injury biomarkers and hydration assessments following prolonged mild hypohydration in healthy young adults.

The high prevalence of inadequate hydration (e.g., hypohydration and underhydration) is concerning given that extreme heat increases excess hospitalizations for fluid/electrolyte disorders and acute kidney injury (AKI). Inadequate hydration may also be related to renal and cardiometabolic disease development. This study tested the hypothesis that prolonged mild hypohydration increases the urinary AKI biomarker product of insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase-2 ([IGFBP7·TIMP-2]) compared with euhydration. In addition, we determined the diagnostic accuracy and optimal cutoffs of hydration assessments for discriminating positive AKI risk ([IGFBP·TIMP-2] >0.3 (ng/mL)2/1,000). In a block-randomized crossover design, 22 healthy young adults (11 females and 11 males) completed 24 h of fluid deprivation (hypohydrated group) or 24 h of normal fluid consumption (euhydrated group) separated by ≥72 h. Urinary [IGFBP7·TIMP-2] and other AKI biomarkers were measured following the 24-h protocols. Diagnostic accuracy was assessed via receiver operating characteristic curve analysis. Urinary [IGFBP7·TIMP-2] [1.9 (95% confidence interval: 1.0-2.8) vs. 0.2 (95% confidence interval: 0.1-0.3) (ng/mL)2/1,000, P = 0.0011] was markedly increased in hypohydrated versus euhydrated groups. Urine osmolality (area under the curve: 0.91, P < 0.0001) and urine specific gravity (area under the curve: 0.89, P < 0.0001) had the highest overall performance for discriminating positive AKI risk. Optimal cutoffs with a positive likelihood ratio of 11.8 for both urine osmolality and specific gravity were 952 mosmol/kgH2O and 1.025 arbitrary units. In conclusion, prolonged mild hypohydration increased urinary [IGFBP7·TIMP-2] in males and females. Urinary [IGFBP7·TIMP-2] corrected to urine concentration was elevated in males only. Urine osmolality and urine specific gravity may have clinical utility for discriminating positive AKI risk following prolonged mild hypohydration.NEW & NOTEWORTHY This study found that prolonged mild hypohydration in healthy young adults increased the Food and Drug Administration approved acute kidney injury (AKI) biomarker urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase-2 [IGFBP7·TIMP-2]. Urine osmolality and specific gravity demonstrated an excellent ability to discriminate positive AKI risk. These findings emphasize the importance of hydration in protecting renal health and lend early support for hydration assessment as an accessible tool to assess AKI risk.

Cardiovascular and mood responses to an acute bout of cold water immersion.

Cold water immersion (CWI) may provide benefits for physical and mental health. Our purpose was to investigate the effects of an acute bout of CWI on vascular shear stress and affect (positive and negative). Sixteen healthy adults (age: 23 ± 4 y; (9 self-reported men and 7 self-reported women) completed one 15-min bout of CWI (10 °C). Self-reported affect (positive and negative) was assessed at pre-CWI (Pre), 30-min post-immersion, and 180-min post-immersion in all participants. Brachial artery diameter and blood velocity were measured (Doppler ultrasound) at Pre, after 1-min and 15-min of CWI, and 30-min post-immersion (n = 8). Total, antegrade, and retrograde shear stress, oscillatory shear index (OSI), and forearm vascular conductance (FVC) were calculated. Venous blood samples were collected at Pre, after 1-min and 15-min of CWI, 30-min post-immersion, and 180-min post-immersion (n = 8) to quantify serum ß-endorphins and cortisol. Data were analyzed using a one-way ANOVA with Fisher's least significance difference and compared to Pre. Positive affect did not change (ANOVA p = 0.450) but negative affect was lower at 180-min post-immersion (p < 0.001). FVC was reduced at 15-min of CWI and 30-min post-immersion (p < 0.020). Total and antegrade shear and OSI were reduced at 30-min post-immersion (p < 0.040) but there were no differences in retrograde shear (ANOVA p = 0.134). ß-endorphins did not change throughout the trial (ANOVA p = 0.321). Cortisol was lower at 180-min post-immersion (p = 0.014). An acute bout of CWI minimally affects shear stress patterns but may benefit mental health by reducing negative feelings and cortisol levels.

Brachial and carotid hemodynamic response to hot water immersion in men and women.

This study sought to compare the brachial and carotid hemodynamic response to hot water immersion (HWI) between healthy young men and women. Ten women (W) and 11 men (M) (24 ± 4 yr) completed a 60-min HWI session immersed to the level of the sternum in 40°C water. Brachial and carotid artery hemodynamics (Doppler ultrasound) were measured at baseline (seated rest) and every 15 min throughout HWI. Within the brachial artery, total shear rate was elevated to a greater extent in women [+479 (+364, +594) s-1] than in men [+292 (+222, +361) s-1] during HWI (P = 0.005). As shear rate is inversely proportional to blood vessel diameter and directly proportional to blood flow velocity, the sex difference in brachial shear response to HWI was the result of a smaller brachial diameter among women at baseline (P < 0.0001) and throughout HWI (main effect of sex, P < 0.0001) and a greater increase in brachial velocity seen in women [+48 (+36, +61) cm/s] compared with men [+35 (+27, +43) cm/s] with HWI (P = 0.047) which allowed for a similar increase in brachial blood flow between sexes [M: +369 (+287, +451) mL/min, W: +364 (+243, +486) mL/min, P = 0.943]. In contrast, no differences were seen between sexes in carotid total shear rate, flow, velocity, or diameter at baseline or throughout HWI. These data indicate the presence of an artery-specific sex difference in the hemodynamic response to a single bout of HWI.

Effects of ACEi and ARB on post-exercise hypotension induced by exercises conducted at different times of day in hypertensive men.

BACKGROUND: Post-exercise hypotension (PEH) is greater after evening than morning exercise, but antihypertensive drugs may affect the evening potentiation of PEH. Objective: To compare morning and evening PEH in hypertensives receiving angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB). METHODS: Hypertensive men receiving ACEi (n = 14) or ARB (n = 15) underwent, in a random order, two maximal exercise tests (cycle ergometer, 15 watts/min until exhaustion) with one conducted in the morning (7 and 9 a.m.) and the other in the evening (8 and 10 p.m.). Auscultatory blood pressure (BP) was assessed in triplicate before and 30 min after the exercises. Changes in BP (post-exercise - pre-exercise) were compared between the groups and the sessions using a two-way mixed ANOVA and considering P < .05 as significant. RESULTS: In the ARB group, systolic BP decrease was greater after the evening than the morning exercise, while in the ACEi group, it was not different after the exercises conducted at the different times of the day. Additionally, after the evening exercise, systolic BP decrease was lower in the ACEi than the ARB group (ARB = -11 ± 8 vs -6 ± 6 and ACEi = -6 ± 7 vs. -8 ± 5 mmHg, evening vs. morning, respectively, P for interaction = 0.014). CONCLUSIONS: ACEi, but not ARB use, blunts the greater PEH that occurs after exercise conducted in the evening than in the morning.

Heat therapy reduces sympathetic activity and improves cardiovascular risk profile in women who are obese with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects up to 15% of women and is associated with increased risk of obesity and cardiovascular disease. Repeated passive heat exposure [termed "heat therapy" (HT)] is a lifestyle intervention with the potential to reduce cardiovascular risk in obesity and PCOS. Women with obesity (n = 18) with PCOS [age 27 ± 4 yr, body mass index (BMI) 41.3 ± 4.7 kg/m2] were matched for age and BMI, then assigned to HT (n = 9) or time control (CON; n = 9). HT subjects underwent 30 one-hour hot tub sessions over 8-10 wk, whereas CON subjects did not undergo HT. Muscle sympathetic nerve activity (MSNA), blood pressure, cholesterol, C-reactive protein, and markers of vascular function were assessed at the start (Pre) and end (Post) of 8-10 wk. These measures included carotid and femoral artery wall thickness and flow-mediated dilation (FMD), measured both before and after 20 min of ischemia-20 min of reperfusion (I/R) stress. HT subjects exhibited reduced MSNA burst frequency (Pre: 20 ± 8 bursts/min, Post: 13 ± 5 bursts/min, P = 0.012), systolic (Pre: 124 ± 5 mmHg, Post: 114 ± 6 mmHg; P < 0.001) and diastolic blood pressure (Pre: 77 ± 6 mmHg, Post: 68 ± 3 mmHg; P < 0.001), C-reactive protein (Pre: 19.4 ± 13.7 nmol/L, Post: 15.2 ± 12.3 nmol/L; P = 0.018), total cholesterol (Pre: 5.4 ± 1.1 mmol/L, Post: 5.0 ± 0.8 mmol/L; P = 0.028), carotid wall thickness (Pre: 0.054 ± 0.005 cm, Post: 0.044 ± 0.005 cm; P = 0.010), and femoral wall thickness (Pre: 0.056 ± 0.009 cm, Post: 0.042 ± 0.005 cm; P = 0.003). FMD significantly improved in HT subjects over time following I/R (Pre: 5.6 ± 2.5%, Post: 9.5 ± 1.7%; P < 0.001). No parameters changed over time in CON, and BMI did not change in either group. These findings indicate that HT reduces sympathetic nerve activity, provides protection from I/R stress, and substantially improves cardiovascular risk profiles in women who are obese with PCOS.

The Intriguing Role of Histamine in Exercise Responses.

In humans, histamine is a molecular transducer of physical activity responses, and antihistamines modify more than 25% of the genes responding to exercise. Although the upstream signal that results in release of histamine within exercising skeletal muscle remains to be identified, it is likely a fundamental exercise response and not an allergic reaction.

Evidence of a broad histamine footprint on the human exercise transcriptome.

KEY POINTS: Histamine is a primordial signalling molecule, capable of activating cells in an autocrine or paracrine fashion via specific cell surface receptors, in a variety of pathways that probably predate its more recent role in innate and adaptive immunity. Although histamine is normally associated with pathological conditions or allergic and anaphylactic reactions, it may contribute beneficially to the normal changes that occur within skeletal muscle during the recovery from exercise. We show that the human response to exercise includes an altered expression of thousands of protein-coding genes, and much of this response appears to be driven by histamine. Histamine may be an important molecular transducer contributing to many of the adaptations that accompany chronic exercise training. ABSTRACT: Histamine is a primordial signalling molecule, capable of activating cells in an autocrine or paracrine fashion via specific cell surface receptors. In humans, aerobic exercise is followed by a post-exercise activation of histamine H1 and H2 receptors localized to the previously exercised muscle. This could trigger a broad range of cellular adaptations in response to exercise. Thus, we exploited RNA sequencing to explore the effects of H1 and H2 receptor blockade on the exercise transcriptome in human skeletal muscle tissue harvested from the vastus lateralis. We found that exercise exerts a profound influence on the human transcriptome, causing the differential expression of more than 3000 protein-coding genes. The influence of histamine blockade post-exercise was notable for 795 genes that were differentially expressed between the control and blockade condition, which represents >25% of the number responding to exercise. The broad histamine footprint on the human exercise transcriptome crosses many cellular functions, including inflammation, vascular function, metabolism, and cellular maintenance.

Effect of antioxidants on histamine receptor activation and sustained postexercise vasodilatation in humans.

NEW FINDINGS: What is the central question of this study? Is exercise-induced oxidative stress the upstream exercise-related signalling mechanism that leads to sustained postexercise vasodilatation via activation of H1 and H2 histamine receptors? What is the main finding and its importance? Systemic administration of the antioxidant ascorbate inhibits sustained postexercise vasodilatation to the same extent as seen previously with H1 and H2 histamine receptor blockade following small muscle-mass exercise. However, ascorbate has a unique ability to catalyse the degradation of histamine. We also found that systemic infusion of the antioxidant N-acetylcysteine had no effect on sustained postexercise vasodilatation, suggesting that exercise-induced oxidative stress does not contribute to sustained postexercise vasodilatation. An acute bout of aerobic exercise elicits a sustained postexercise vasodilatation that is mediated by histamine H1 and H2 receptor activation. However, the upstream signalling pathway that leads to postexercise histamine receptor activation is unknown. We tested the hypothesis that the potent antioxidant ascorbate would inhibit this histaminergic vasodilatation following exercise. Subjects performed 1 h of unilateral dynamic knee extension at 60% of peak power in three conditions: (i) control; (ii) i.v. ascorbate infusion; and (iii) ascorbate infusion plus oral H1 /H2 histamine receptor blockade. Femoral artery blood flow was measured (using Doppler ultrasound) before exercise and for 2 h postexercise. Femoral vascular conductance was calculated as flow/pressure. Postexercise vascular conductance was greater for control conditions (3.4 ± 0.1 ml min(-1) mmHg(-1) ) compared with ascorbate (2.7 ± 0.1 ml min(-1) mmHg(-1) ; P < 0.05) and ascorbate plus H1 /H2 blockade (2.8 ± 0.1 ml min(-1) mmHg(-1) ; P < 0.05), which did not differ from one another (P = 0.9). Given that ascorbate may catalyse the degradation of histamine in vivo, we conducted a follow-up study, in which subjects performed exercise in two conditions: (i) control; and (ii) i.v. N-acetylcysteine infusion. Postexercise vascular conductance was similar for control (4.0 ± 0.1 ml min(-1) mmHg(-1) ) and N-acetylcysteine conditions (4.0 ± 0.1 ml min(-1) mmHg(-1) ; P = 0.8). Thus, the results in the initial study were due to the degradation of histamine in skeletal muscle by ascorbate, because the histaminergic vasodilatation was unaffected by N-acetylcysteine. Overall, exercise-induced oxidative stress does not appear to contribute to sustained postexercise vasodilatation.

Increased cardiac output, not pulmonary artery systolic pressure, increases intrapulmonary shunt in healthy humans breathing room air and 40% O2.

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) has been demonstrated to increase in healthy humans during a variety of conditions; however, whether or not this blood flow represents a source of venous admixture (Q̇ VA /Q̇T) that impairs pulmonary gas exchange efficiency (i.e. increases the alveolar-to-arterial PO2 difference (A-aDO2)) remains controversial and unknown. We hypothesized that blood flow through IPAVAs does provide a source of Q̇ VA /Q̇T. To test this, blood flow through IPAVAs was increased in healthy humans at rest breathing room air and 40% O2: (1) during intravenous adrenaline (epinephrine) infusion at 320 ng kg(-1) min(-1) (320 ADR), and (2) with vagal blockade (2 mg atropine), before and during intravenous adrenaline infusion at 80 ng kg(-1) min(-1) (ATR + 80 ADR). When breathing room air the A-aDO2 increased by 6 ± 2 mmHg during 320 ADR and by 5 ± 2 mmHg during ATR + 80 ADR, and the change in calculated Q̇ VA /Q̇T was +2% in both conditions. When breathing 40% O2, which minimizes contributions from diffusion limitation and alveolar ventilation-to-perfusion inequality, the A-aDO2 increased by 12 ± 7 mmHg during 320 ADR, and by 9 ± 6 mmHg during ATR + 80 ADR, and the change in calculated Q̇ VA /Q̇T was +2% in both conditions. During 320 ADR cardiac output (Q̇T) and pulmonary artery systolic pressure (PASP) were significantly increased; however, during ATR + 80 ADR only Q̇T was significantly increased, yet blood flow through IPAVAs as detected with saline contrast echocardiography was not different between conditions. Accordingly, we suggest that blood flow through IPAVAs provides a source of intrapulmonary shunt, and is mediated primarily by increases in Q̇T rather than PASP.

Postexercise syncope: Wingate syncope test and effective countermeasure.

Altered systemic haemodynamics following exercise can compromise cerebral perfusion and result in syncope. As the Wingate anaerobic test often induces presyncope, we hypothesized that a modified Wingate test could form the basis of a novel model for the study of postexercise syncope and a test bed for potential countermeasures. Along these lines, breathing through an impedance threshold device has been shown to increase tolerance to hypovolaemia, and could prove beneficial in the setting of postexercise syncope. Therefore, we hypothesized that a modified Wingate test followed by head-up tilt would produce postexercise syncope, and that breathing through an impedance threshold device (countermeasure) would prevent postexercise syncope in healthy individuals. Nineteen recreationally active men and women underwent a 60 deg head-up tilt during recovery from the Wingate test while arterial pressure, heart rate, end-tidal CO2 and cerebral tissue oxygenation were measured on a control day and a countermeasure day. The duration of tolerable tilt was increased by a median time of 3 min 48 s with countermeasure in comparison to the control (P < 0.05), and completion of the tilt test increased from 42 to 67% with the countermeasure. During the tilt, mean arterial pressure was greater (108.0 ± 4.1 versus 100.4 ± 2.4 mmHg; P < 0.05) with the countermeasure in comparison to the control. These data suggest that the Wingate syncope test produces a high incidence of presyncope, which is sensitive to countermeasures such as inspiratory impedance.

Blood pressure regulation X: what happens when the muscle pump is lost? Post-exercise hypotension and syncope.

Syncope which occurs suddenly in the setting of recovery from exercise, known as post-exercise syncope, represents a failure of integrative physiology during recovery from exercise. We estimate that between 50 and 80% of healthy individuals will develop pre-syncopal signs and symptoms if subjected to a 15-min head-up tilt following exercise. Post-exercise syncope is most often neurally mediated syncope during recovery from exercise, with a combination of factors associated with post-exercise hypotension and loss of the muscle pump contributing to the onset of the event. One can consider the initiating reduction in blood pressure as the tip of the proverbial iceberg. What is needed is a clear model of what lies under the surface; a model that puts the observational variations in context and provides a rational framework for developing strategic physical or pharmacological countermeasures to ultimately protect cerebral perfusion and avert loss of consciousness. This review summarizes the current mechanistic understanding of post-exercise syncope and attempts to categorize the variation of the physiological processes that arise in multiple exercise settings. Newer investigations into the basic integrative physiology of recovery from exercise provide insight into the mechanisms and potential interventions that could be developed as countermeasures against post-exercise syncope. While physical counter maneuvers designed to engage the muscle pump and augment venous return are often found to be beneficial in preventing a significant drop in blood pressure after exercise, countermeasures that target the respiratory pump and pharmacological countermeasures based on the involvement of histamine receptors show promise.

Effect of histamine-receptor antagonism on the circulating inflammatory cell and cytokine response to exercise: A pilot study.

The purpose of this study was to gain insight into histamine's role in the exercise inflammatory response and recovery from exercise. To explore this, young healthy participants (n = 12) performed 300 eccentric leg extensions under control (Placebo) versus histamine H1 and H2 receptor antagonism (Blockade) in a randomized cross-over study. Circulating leukocytes and cytokines were measured for 72 h after exercise. Circulating leukocytes were elevated at 6 and 12 h after exercise (p < 0.05) with the peak response being a 44.1 ± 11.7% increase with Blockade versus 13.7 ± 6.6% with Placebo (both p < 0.05 vs. baseline, but also p < 0.05 between Blockade and Placebo). Of the cytokines that were measured, only MCP-1 was elevated following exercise. The response at 6 h post-exercise was a 104.0 ± 72.5% increase with Blockade versus 93.1 ± 41.9% with Placebo (both p < 0.05 vs. baseline, p = 0.82 between Blockade and Placebo). The main findings of the present investigation were that taking combined histamine H1 and H2 receptor antagonists augmented the magnitude but not the duration of the increase of circulating immune cells following exercise. This suggests histamine is not only exerting a local influence within the skeletal muscle but that it may influence the systemic inflammatory patterns.

Hypohydration attenuates increases in creatinine clearance to oral protein loading and the renal hemodynamic response to exercise pressor reflex.

Insufficient hydration is prevalent among free living adults. This study investigated whether hypohydration alters 1) renal functional reserve, 2) the renal hemodynamic response to the exercise pressor reflex, and 3) urine-concentrating ability during oral protein loading. In a block-randomized crossover design, 22 healthy young adults (11 females and 11 males) underwent 24-h fluid deprivation (Hypohydrated) or 24-h normal fluid consumption (Euhydrated). Renal functional reserve was assessed by oral protein loading. Renal hemodynamics during the exercise pressor reflex were assessed via Doppler ultrasound. Urine-concentrating ability was assessed via free water clearance. Creatinine clearance did not differ at 150 min postprotein consumption between conditions [Hypohydrated: 246 mL/min, 95% confidence interval (CI): 212-280; Euhydrated: 231 mL/min, 95% CI: 196-265, P = 0.2691] despite an elevated baseline in Hypohydrated (261 mL/min, 95% CI: 218-303 vs. 143 mL/min, 95% CI: 118-168, P < 0.0001). Renal artery vascular resistance was not different at baseline (P = 0.9290), but increases were attenuated in Hypohydrated versus Euhydrated at the end of handgrip (0.5 mmHg/cm/s, 95% CI: 0.4-0.7 vs. 0.8 mmHg/cm/s 95% CI: 0.6-1.1, P = 0.0203) and end occlusion (0.2 mmHg/cm/s, 95% CI: 0.1-0.3 vs. 0.4 mmHg/cm/s 95% CI: 0.3-0.6, P = 0.0127). There were no differences between conditions in free water clearance at 150 min postprotein (P = 0.3489). These data indicate that hypohydration 1) engages renal functional reserve and attenuates the ability to further increase creatinine clearance, 2) attenuates increases in renal artery vascular resistance to the exercise pressor reflex, and 3) does not further enhance nor impair urine-concentrating ability during oral protein loading.NEW & NOTEWORTHY Insufficient hydration is prevalent among free living adults. This study found that hypohydration induced by 24-h fluid deprivation engaged renal functional reserve and that oral protein loading did not further increase creatinine clearance. Hypohydration also attenuated the ability to increase renal vascular resistance during the exercise pressor reflex. In addition, hypohydration neither enhanced nor impaired urine-concentrating ability during oral protein loading. These data support the importance of mitigating hypohydration in free living adults.

Short-term administration of progesterone and estradiol independently alter carotid-vasomotor, but not carotid-cardiac, baroreflex function in young women.

The individual effects of estrogen and progesterone on baroreflex function remain poorly understood. We sought to determine how estradiol (E2) and progesterone (P4) independently alter the carotid-cardiac and carotid-vasomotor baroreflexes in young women by using a hormone suppression and exogenous add-back design. Thirty-two young women were divided into two groups and studied under three conditions: 1) after 4 days of endogenous hormone suppression with a gonadotropin releasing hormone antagonist (control condition), 2) after continued suppression and 3 to 4 days of supplementation with either 200 mg/day oral progesterone (N = 16) or 0.1 to 0.2 mg/day transdermal 17ß-estradiol (N = 16), and 3) after continued suppression and 3 to 4 days of supplementation with both hormones. Changes in heart rate (HR), mean arterial pressure (MAP), and femoral vascular conductance (FVC) were measured in response to 5 s of +50 mmHg external neck pressure to unload the carotid baroreceptors. Significant hormone effects on the change in HR, MAP, and FVC from baseline at the onset of neck pressure were determined using mixed model covariate analyses accounting for P4 and E2 plasma concentrations. Neither P4 (P = 0.95) nor E2 (P = 0.95) affected the HR response to neck pressure. Higher P4 concentrations were associated with an attenuated fall in FVC (P = 0.01), whereas higher E2 concentrations were associated with an augmented fall in FVC (P = 0.02). Higher E2 was also associated with an augmented rise in MAP (P = 0.01). We conclude that progesterone blunts whereas estradiol enhances carotid-vasomotor baroreflex sensitivity, perhaps explaining why no differences in sympathetic baroreflex sensitivity are commonly reported between low and high combined hormone phases of the menstrual cycle.

Sustained postexercise vasodilatation and histamine receptor activation following small muscle-mass exercise in humans.

A sustained postexercise vasodilatation, which is histamine receptor mediated, has been observed following single bouts of whole-body exercise, but the mechanisms that regulate activation of histamine receptors following exercise are undefined. Exploration of vasodilatation after small muscle-mass dynamic or resistance exercise could provide novel insight into the pathways responsible for histamine receptor activation. We hypothesized that there would be a vasodilatation of the previously exercised limb following small muscle-mass dynamic and resistance exercise, which would be mediated by histamine receptors. We studied men and women before and after single-leg dynamic (n = 9) or resistance knee-extension exercise (n = 12) on control and blockade days (combined oral H(1) and H(2) receptor antagonism with fexofenadine and ranitidine). We measured arterial blood pressure (automated brachial oscillometry) and femoral artery blood flow (Doppler ultrasound). Dynamic exercise elevated leg vascular conductance in the active leg by 27.2 ± 8.4% at 60 min postexercise (P < 0.05 versus pre-exercise), but did not alter conductance in the rested leg (change, 4.6 ± 3.5%; P = 0.8 versus pre-exercise). The rise in conductance was abolished on the blockade day (change, 3.7 ± 5.1%; P = 0.8 versus pre-exercise, P = 0.2 versus control). Resistance exercise did not produce a sustained vasodilatation (change, -4.3 ± 4.7% at 60 min postexercise; P = 0.7 versus pre-exercise). These data indicate that histamine receptors are activated following dynamic, but not resistance, exercise. Furthermore, these data suggest that local factors associated with aerobic exercise, and not systemic factors or factors associated with high muscle force, are responsible for activation of histamine receptors in the previously exercised muscle.

Postexercise hypotension and sustained postexercise vasodilatation: what happens after we exercise?

A single bout of aerobic exercise produces a postexercise hypotension associated with a sustained postexercise vasodilatation of the previously exercised muscle. Work over the last few years has determined key pathways for the obligatory components of postexercise hypotension and sustained postexercise vasodilatation and points the way to possible benefits that may result from these robust responses. During the exercise recovery period, the combination of centrally mediated decreases in sympathetic nerve activity with a reduced signal transduction from sympathetic nerve activation into vasoconstriction, as well as local vasodilator mechanisms, contributes to the fall in arterial blood pressure seen after exercise. Important findings from recent studies include the recognition that skeletal muscle afferents may play a primary role in postexercise resetting of the baroreflex via discrete receptor changes within the nucleus tractus solitarii and that sustained postexercise vasodilatation of the previously active skeletal muscle is primarily the result of histamine H(1) and H(2) receptor activation. Future research directions include further exploration of the potential benefits of these changes in the longer term adaptations associated with exercise training, as well as investigation of how the recovery from exercise may provide windows of opportunity for targeted interventions in patients with hypertension and diabetes.