[show abstract][hide abstract] ABSTRACT: Ultrasound Doppler and near infrared spectroscopy (NIRS) are routinely used for non-invasive monitoring of peripheral hemodynamics in both clinical and experimental settings. However, the comparative ability of these methodologies to detect changes in microvascular and whole-limb hemodynamics during pharmacologic manipulation of vascular smooth muscle receptors located at varied locations within the arterial tree is unknown. Thus, in ten healthy subjects (25±2 yrs), changes in resting leg blood flow (Ultrasound Doppler; femoral artery) and muscle oxygenation (HbO2+MbO2; vastus lateralis) were evaluated simultaneously in response to intra-arterial infusions of phenylephrine (PE, 0.025 - 0.8 μg/kg/min), BHT-933 (2.5 - 40 µg/kg/min), and angiotensin II (ANGII, 0.5 - 8 ng/kg/min). All drugs elicited significant dose-dependent reductions in leg blood flow and HbO2+MbO2. Significant relationships were found between ultrasound Doppler and NIRS changes across doses of PE (r(2) = 0.37±0.08), BHT-933 (r(2) = 0.74±0.06), and ANGII (r(2) = 0.68±0.13), with the strongest relationships evident with agonists for receptors located preferentially "downstream" in the leg microcirculation (BHT-933 and ANGII). Analyses of drug potency revealed similar EC50 between ultrasound Doppler and NIRS measurements for PE (0.06±0.02 vs. 0.10±0.01), BHT-933 (5.0±0.9 vs. 4.5±1.3), and ANGII (1.4±0.8 vs. 1.3±0.3). These data provide evidence that both ultrasound Doppler and NIRS track pharmacologically-induced changes in peripheral hemodynamics, and are equally capable of determining drug potency. However, considerable disparity was observed between agonist infusions targeting different levels of the arterial tree, suggesting that receptor landscape is an important consideration for proper interpretation of hemodynamic monitoring with these methodologies.
AJP Heart and Circulatory Physiology 01/2014; · 3.63 Impact Factor
[show abstract][hide abstract] ABSTRACT: Animal studies have suggested that functional sympatholysis was effected by muscle fiber type such that it appeared to occur preferentially in glycolytic (largely Type II) compared to oxidative (largely Type I) skeletal muscle. Whether these findings can be extended to humans currently remains unclear. In twelve healthy male subjects, vasoconstrictor responses in gastrocnemius (i.e., primarily Type II) and soleus (i.e., primarily Type I) muscles were measured using near infrared spectroscopy to detect decreases in muscle oxygenation (HbO2) in response to sympathetic activation evoked by a cold pressor test (CPT). HbO2 responses to CPT at rest were compared to responses during steady-state plantar flexion exercise (30 repetitions/min) performed at 10%, 20%, and 40% maximal voluntary contraction (MVC) for 6 min. Under resting conditions, HbO2 at the gastrocnemius (-14±1%) and soleus muscles (-16±1%) significantly decreased during CPT with no differences between muscles. During planter flexion at 20% MVC, the change in HbO2 in response to the CPT was blunted in gastrocnemius but not soleus, whereas during 40% MVC both muscles exhibited a significant attenuation to sympathetic activation. The decreases in HbO2 to CPT during exercise were significantly correlated to the metabolic demand of exercise (the decreases in HbO2 to steady-state plantar flexion) in both gastrocnemius and soleus muscles. Collectively, these results suggest skeletal muscle composed of greater glycolytic Type II fibers are more sensitive to functional sympatholysis, particularly at lower intensities of exercise. Moreover, the blunting of sympathetic vasoconstriction during exercise was strongly related to metabolic demand; an effect that appeared independent of fiber type composition.
[show abstract][hide abstract] ABSTRACT: Physical inactivity promotes the development of cardiovascular diseases. However, few data exist examining the vascular consequences of short-term reductions in daily physical activity. Thus, we tested the hypothesis that popliteal and brachial artery flow-mediated dilation (FMD) would be reduced and concentrations of endothelial microparticles (EMPs) would be elevated following reduced daily physical activity. To examine this, popliteal and brachial artery FMD and plasma levels of EMPs suggestive of apoptotic and activated endothelial cells (CD31(+)/CD42b(-) and CD62E(+) EMPs, respectively) were measured at baseline and during days 1,3, and 5 of reduced daily physical activity in 11 recreationally active men (25±2 yrs). Subjects were instructed to reduce daily physical activity by taking <5,000 steps/day and refraining from planned exercise. Popliteal artery FMD decreased with reduced activity (Baseline: 4.7±0.98%, Reduced Activity Day 5: 1.72±0.68%, p<0.05), while brachial artery FMD was unchanged. In contrast, baseline (pre FMD) popliteal artery diameter did not change whereas, brachial artery diameter decreased (Baseline: 4.35±0.12, Reduced Activity Day 5: 4.12±0.11 p<0.05) following 5 days of reduced daily physical activity. CD31(+)/CD42b(-) EMPs were significantly elevated with reduced activity (Baseline: 17.6 ± 9.4, Reduced Activity Day 5: 104.1±43.1 per μL plasma, p<0.05), whereas CD62E(+) EMPs were unaltered. Collectively, our results provide evidence for the early and robust deleterious impact of reduced daily activity on vascular function and highlight the vulnerability of the vasculature to a sedentary lifestyle.
Journal of Applied Physiology 09/2013; · 3.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: Many diseases associated with sympathoexcitation also exhibit elevated reactive oxygen species (ROS). A recent animal study indicated that exogenous administration of the sympathetic neurotransmitter, norepinephrine (NE), increased systemic ROS via circulating leukocytes. The mechanisms contributing to this effect of NE and whether these findings can be translated to humans is unknown. Thus, we tested the hypothesis that NE increases superoxide production in human peripheral blood mononuclear cells (PBMCs) via NADPH oxidase. Primary human PBMCs were freshly isolated from healthy young men and placed in culture. Following NE (50pg/ml, 50ng/ml and 50µg/ml concentrations) or control treatments, NADPH oxidase mRNA expression (gp91(phox), p22(phox) and p67(phox)) was assessed using real time RT-PCR and intracellular superoxide production was measured using dihydroethidium fluorescence. PBMCs were also treated with selective adrenergic agonists-antagonists to determine the receptor population involved. In addition, CD14(+) monocyte-endothelial cell adhesion was determined using a fluorescent-based assay. NE significantly increased NADPH oxidase gene expression and intracellular superoxide production in a time dependent manner (superoxide: 0.9±0.2 fold 6 hours vs. 3.0±0.3 fold 36 hours (NE, 50μg/ml); P < 0.05). The sustained increase in NE-induced superoxide production was primarily mediated via α-adrenergic receptors, preferentially α2-receptors. The NADPH oxidase blocker diphenylene iodonium and protein kinase C inhibitor staurosporine significantly attenuated NE-induced increases in superoxide production. Importantly, NE treatment increased CD14(+) monocyte-endothelial cell adhesion. These findings indicate for the first time that NE increases superoxide production in freshly isolated primary human PBMCs via NADPH oxidase through α-adrenergic receptors; an effect facilitating monocyte adhesion to the endothelium.
[show abstract][hide abstract] ABSTRACT: Near-infrared spectroscopy (NIRS) is widely used to investigate cerebral oxygenation and/or neural activation during physiological conditions such as exercise. However, NIRS-determined cerebral oxygenated hemoglobin (O2Hb) may not necessarily correspond to intracranial blood flow during dynamic exercise. To determine the selectivity of NIRS to assess cerebral oxygenation and neural activation during exercise, we examined the influence of changes in forehead skin blood flow (SkBFhead) on NIRS signals during dynamic exercise.
In ten healthy men (age: 20 ± 1 years), middle cerebral artery blood flow velocity (MCA V mean, via transcranial Doppler ultrasonography), SkBFhead (via laser Doppler flowmetry), and cerebral O2Hb (via NIRS) were continuously measured. Each subject performed 60 % maximum heart rate moderate-intensity steady-state cycling exercise. To manipulate SkBFhead, facial cooling using a mist of cold water (~4 °C) was applied for 3 min during steady-state cycling.
MCA V mean significantly increased during exercise and remained unchanged with facial cooling. O2Hb and SkBFhead were also significantly increased during exercise; however, both of these signals were lowered with facial cooling and returned to pre-cooling values with the removal of facial cooling. The changes in O2Hb correlated significantly with the relative percent changes in SkBFhead in each individual (r = 0.71-0.99).
These findings suggest that during dynamic exercise NIRS-derived O2Hb signal can be influenced by thermoregulatory changes in SkBFhead and therefore, may not be completely reflective of cerebral oxygenation or neural activation.
[show abstract][hide abstract] ABSTRACT: Dysfunction of the endothelium is proposed as the primary initiator of atherosclerotic peripheral artery disease, which occurs mainly in medium- to large-sized conduit arteries of the lower extremities (e.g., iliac, femoral, popliteal arteries). In this review article, we propose the novel concept that conduit artery endothelial cell phenotype is determined, in part, by microvascular tone in skeletal muscle resistance arteries through both changes in arterial blood pressure as well as upstream conduit artery shear stress patterns. First, we summarize the literature supporting the involvement of sympathetic nerve activity (SNA) and nitric oxide (NO) in the modulation of microvascular tone and arterial blood pressure. We then focus on the role of elevated blood pressure and shear stress profiles in modulating conduit artery endothelial cell phenotype. Last, we discuss findings from classic and emerging studies indicating that increased vascular resistance, as it occurs in the context of increased SNA and/or reduced NO bioavailability, is associated with greater oscillatory shear stress (e.g., increased retrograde shear) in upstream conduit arteries. The ideas put forth in this review set the stage for a new paradigm concerning the mechanistic link between increased microvascular tone and development of conduit artery endothelial dysfunction and thus increased risk for peripheral artery disease. Indeed, a vast amount of evidence supports the notion that excessive blood pressure and oscillatory shear stress are potent pro-atherogenic signals to the endothelium.
[show abstract][hide abstract] ABSTRACT: Large increases in muscle sympathetic nerve activity (MSNA) can decrease the diameter of a conduit artery even in the presence of elevated blood pressure, suggesting that MSNA acts to regulate conduit artery tone. Whether this influence can be extrapolated to spontaneously occurring MSNA bursts has not been examined. Therefore, we tested the hypothesis that MSNA bursts decrease conduit artery diameter on a beat-by-beat basis during rest. Conduit artery responses were assessed in the brachial (BA), common femoral (CFA) and popliteal (PA) arteries to account for regional differences in vascular function. In 20 young men, MSNA, mean arterial pressure (MAP), conduit artery diameter and shear rate (SR) were continuously measured during 20 min periods of supine rest. Spike-triggered averaging was used to characterize beat-by-beat changes in each variable for 15 cardiac cycles following all MSNA bursts, and a peak response was calculated. Diameter increased to a similar peak among the BA (+0.14±0.02%), CFA (+0.17±0.03%), and PA (+0.18±0.03%) following MSNA bursts (all P<0.05 vs. control). The diameter rise was positively associated with an increase in MAP in relation with increasing amplitude and consecutive numbers of MSNA bursts (P<0.05). Such relationships were similar between arteries. SR changes following MSNA bursts were heterogeneous between arteries and did not appear to systematically alter diameter responses. Thus, in contrast to our hypothesis, spontaneously occurring MSNA bursts do not directly influence conduit arteries with local vasoconstriction or changes in shear, but rather induce a systemic pressor response that appears to passively increase conduit artery diameter.
AJP Heart and Circulatory Physiology 07/2013; · 3.63 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sympathetic baroreflex sensitivity is increased during selective activation of the skeletal muscle metaboreflex with post-exercise ischemia (PEI) in young adults. However, to date, there are no data demonstrating this neural interaction between the arterial baroreflex and the muscle metaboreflex in healthy older adults. Therefore, the goal of the current study was to examine the influence of healthy aging on the metabolic component of the exercise pressor reflex and its interaction with the arterial baroreflex in the control of sympathetic outflow. PEI following static handgrip performed at 30% maximum voluntary contraction was used to isolate muscle metaboreflex activation in young (n=10; 24±1 yrs; resting blood pressure (BP) 116±3/64±3 mmHg) and older men (n=9; 59±2 yrs; resting BP 120±2/77±2 mmHg). Arterial BP (Finometer) and muscle sympathetic nerve activity (MSNA) were measured continuously. Weighted linear regression analysis between MSNA and diastolic BP was used to estimate arterial baroreflex MSNA gain. There were no age-related differences in the increase in mean BP (14±3 young vs. 15±2 older mmHg; P>0.05) or MSNA burst frequency (11±2 young vs. 9±1 older bursts/min; P>0.05) during PEI. Likewise, the gain of arterial baroreflex control of total MSNA increased to a similar extent in both groups during PEI (young: -4.2±0.9 baseline vs. -6.3±1.1 PEI AU/beat/mmHg; older: -3.7±1.1 baseline vs. -6.7±1.4 PEI AU/beat/mmHg; P<0.05 for both). Collectively, these findings indicate that the neural interaction between the arterial baroreflex and the skeletal muscle metaboreflex in the regulation of MSNA is preserved in healthy aging.
[show abstract][hide abstract] ABSTRACT: Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α-adrenergic receptor-mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during 20 minutes of supine rest. These measures were also recorded in 7 men during intra-arterial infusions of normal saline (SAL), phentolamine (PHEN), and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α-adrenergic blockade. Spike-triggered averaging was used to characterize beat-by-beat changes in FVC for 15 cardiac cycles following each individual MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3±0.3% (P=0.016) and then robustly decreased to a nadir of -5.8±1.6% (P<0.001). The magnitude of vasoconstriction appeared graded with number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (-2.1±0.7% and -0.7±0.8%, respectively; P<0.001 vs. SAL). These findings indicate that spontaneous MSNA bursts evoke robust beat-by-beat decreases in FVC that are exclusively mediated via α-adrenergic receptors.
The Journal of Physiology 05/2013; · 4.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVES: Determine if simvastatin impairs exercise training adaptations. BACKGROUND: Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with the metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training. METHODS: We examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg per day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity). RESULTS: Thirty-seven participants (exercise plus statins; n=18; exercise only; n=19) completed the study. Cardiorespiratory fitness increased by 10% (P<0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (P<0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise only group (P <0.05), but decreased by 4.5% in the simvastatin plus exercise group (P<0.05 for group by time interaction). CONCLUSION: Simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome.
Journal of the American College of Cardiology 04/2013; · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is strong and consistent evidence from in vitro studies that disturbed blood flow produces a proatherogenic vascular endothelial phenotype. However, data from human studies are lacking. To address this, a 220 mm Hg occlusion cuff was placed on the distal forearm of 10 young, healthy men to induce a localized region of disturbed blood flow in the proximal vasculature for 20 minutes. We hypothesized that disturbed blood flow would induce endothelial activation and apoptosis as indicated by increases in local concentrations of CD62E(+) and CD31(+)/CD42b(-) endothelial microparticles, respectively. Distal cuff occlusion induced reductions in mean blood flow, mean shear, and antegrade shear, and increases in retrograde flow, retrograde shear, and oscillatory shear stress, confirming that our protocol produced a disturbed blood flow stimulus in the experimental arm. Relative to baseline (0 minutes), CD62E(+) endothelial microparticles increased by ≈3-fold at 10 minutes and ≈4-fold at 20 minutes in the experimental arm (P<0.05). CD31(+)/CD42b(-) endothelial microparticles were elevated by ≈9-fold at the 20 minutes time point (P<0.05). There were no changes in the concentrations of either endothelial microparticle population throughout the experiment in the contralateral arm, exposed to normal resting blood flow (no cuffs). These findings indicate that disturbed blood flow acutely induces endothelial activation and apoptosis in humans, as reflected by release of microparticles from activated (CD62E(+)) and apoptotic (CD31(+)/CD42b(-)) endothelial cells. These data provide the first in vivo experimental evidence of disturbed blood flow-induced endothelial injury in humans.
[show abstract][hide abstract] ABSTRACT: Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus, we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single vs. multiple bursts) and burst size may affect the magnitude of the LVC response. In 11 young men, arterial blood pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 minutes of supine rest. Signal averaging was used to characterize percent changes in LVC for 15 cardiac cycles following heartbeats associated with and without MSNA bursts. LVC significantly decreased following MSNA bursts, reaching a nadir during the 6th cardiac cycle (single bursts: -2.9±1.1%; multiple bursts -11.0±1.4%; both P<0.001). Individual MSNA burst amplitudes and the total amplitude of consecutive bursts were related to the magnitude of peak decreases in LVC. In contrast, cardiac cycles without MSNA bursts were associated with a significant increase in LVC (+3.1±0.5%; P<0.001). Total vascular conductance decreased in parallel with LVC also reaching a nadir around the peak rise in arterial blood pressure following an MSNA burst. Collectively, these data are the first to assess beat-by-beat sympathetic vascular transduction in resting humans, demonstrating robust and dynamic decreases in LVC following MSNA bursts; an effect that was absent for cardiac cycles without MSNA bursts.
AJP Heart and Circulatory Physiology 01/2013; · 3.63 Impact Factor
[show abstract][hide abstract] ABSTRACT: The arterial baroreflex (ABR) performs an important role in regulating blood pressure (BP) both at rest and during exercise, by carefully orchestrating autonomic neural activity to the heart and blood vessels. Reduced ABR sensitivity (i.e., gain) has been associated with increased cardiovascular risk, cardiac electrical instability and orthostatic intolerance, while 'normal' ABR function during exercise is important for ensuring an appropriate cardiovascular response is elicited. Previous studies examining the influence of age and sex on resting ABR function in humans have primarily used pharmacological methods (e.g., modified Oxford technique) to change BP and alter baroreceptor input. With this approach only reflex control of heart rate and sympathetic nerve activity may be evaluated, and as such the influence of age and sex on ABR control of BP per se remains incompletely understood. Furthermore, the majority of previous studies examining ABR function during exercise have principally assessed young men. Whether these findings can be extrapolated to young women or older men and women remains unclear. Recently the potential for age and sex to modulate the integrative neural control of the cardiovascular system is becoming appreciated. This review article will provide a detailed update of such recent advances into our understanding of the effects of age and sex on ABR control of BP both at rest and during dynamic exercise in humans.
[show abstract][hide abstract] ABSTRACT: Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in heart failure (HF) patients making the sympathetic nervous system a primary drug target in the treatment of HF. Studies in rabbits with pacing-induced HF have demonstrated that statins reduce resting SNA, in part, due to reductions in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF remains unclear. We first performed a study in seven statin-naïve HF patients (56 ± 2 yr; ejection fraction: 31 ± 4%) to determine if 1 mo of simvastatin (40 mg/day) reduces muscle SNA (MSNA). Next, to control for possible placebo effects and determine the effect of simvastatin on ROS, a double-blinded, placebo-controlled crossover design study was performed in six additional HF patients (51 ± 3 yr; ejection fraction: 22 ± 4%), and MSNA, ROS, and superoxide were measured. We tested the hypothesis that statin therapy decreases resting MSNA in HF patients and this would be associated with reductions in ROS. In study 1, simvastatin reduced resting MSNA (75 ± 5 baseline vs. 65 ± 5 statin bursts/100 heartbeats; P < 0.05). Likewise, in study 2, simvastatin also decreased resting MSNA (59 ± 5 placebo vs. 45 ± 6 statin bursts/100 heartbeats; P < 0.05). In addition, statin therapy significantly reduced total ROS and superoxide. As expected, cholesterol was reduced after simvastatin. Collectively, these findings indicate that short-term statin therapy concomitantly reduces resting MSNA and total ROS and superoxide in HF patients. Thus, in addition to lowering cholesterol, statins may also be beneficial in reducing sympathetic overactivity and oxidative stress in HF patients.
[show abstract][hide abstract] ABSTRACT: The sympathetic nervous system is critical for the beat-to-beat regulation of arterial blood pressure (BP). Although studies have examined age- and sex-related effects on BP control, findings are inconsistent and limited data are available in postmenopausal women. In addition, the majority of studies have focused on time-averaged responses without consideration for potential beat-to-beat alterations. Thus we examined whether the ability of muscle sympathetic nerve activity (MSNA) to modulate BP on a beat-to-beat basis is affected by age or sex. BP and MSNA were measured during supine rest in 40 young (20 men) and 40 older (20 men) healthy subjects. Beat-to-beat fluctuations in mean arterial pressure (MAP) were characterized for 15 cardiac cycles after each MSNA burst using signal averaging. The rise in MAP following an MSNA burst was similar between young men and women (+2.64 ± 0.3 vs. +2.57 ± 0.3 mmHg, respectively). However, the magnitude of the increase in MAP after an MSNA burst was reduced in older compared with young subjects (P < 0.05). Moreover, the attenuation of the pressor response was greater in older women (+1.20 ± 0.1 mmHg) compared with older men (+1.72 ± 0.2 mmHg; P < 0.05). Interestingly, in all groups, MAP consistently decreased after cardiac cycles without MSNA bursts (nonbursts) with the magnitude of fall greatest in older men. In summary, healthy aging is associated with an attenuated beat-to-beat increase in BP after a spontaneous MSNA burst, and this attenuation is more pronounced in postmenopausal women. Furthermore, our nonburst findings highlight the importance of sympathetic vasoconstrictor activity to maintain beat-to-beat BP, particularly in older men.
[show abstract][hide abstract] ABSTRACT: To date, no studies have examined whether there are either sex- or ovarian hormone-related alterations in arterial baroreflex resetting and function during dynamic exercise. Thus we studied 16 young men and 18 young women at rest and during leg cycling at 50% heart rate (HR) reserve. In addition, 10 women were studied at three different phases of the menstrual cycle. Five-second pulses of neck pressure (NP) and neck suction (NS) from +40 to -80 Torr were applied to determine full carotid baroreflex (CBR) stimulus response curves. An upward and rightward resetting of the CBR function curve was observed during exercise in all groups with a similar magnitude of CBR resetting for mean arterial pressure (MAP) and HR between sexes (P > 0.05) and at different phases of the menstrual cycle (P > 0.05). For CBR control of MAP, women exhibited augmented pressor responses to NP at rest and exercise during mid-luteal compared with early and late follicular phases. For CBR control of HR, there was a greater bradycardic response to NS in women across all menstrual cycle phases with the operating point (OP) located further away from centering point (CP) on the CBR-HR curve during rest (OP-CP; in mmHg: -13 ± 3 women vs. -3 ± 3 men; P < 0.05) and exercise (in mmHg: -31 ± 2 women vs. -15 ± 3 men; P < 0.05). Collectively, these findings suggest that sex and fluctuations in ovarian hormones do not influence exercise resetting of the baroreflex. However, women exhibited greater CBR control of HR during exercise, specifically against acute hypertension, an effect that was present throughout the menstrual cycle.
Journal of Applied Physiology 01/2012; 112(8):1361-71. · 3.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: After considerable debate and key experimental evidence, the importance of the arterial baroreflex in contributing to and maintaining the appropriate neural cardiovascular adjustments to exercise is now well accepted. Indeed, the arterial baroreflex resets during exercise in an intensity-dependent manner to continue to regulate blood pressure as effectively as at rest. Studies have indicated that the exercise resetting of the arterial baroreflex is mediated by both the feedforward mechanism of central command and the feedback mechanism associated with skeletal muscle afferents (the exercise pressor reflex). Another perhaps less appreciated neural mechanism involved in evoking and maintaining neural cardiovascular responses to exercise is the cardiopulmonary baroreflex. The limited information available regarding the cardiopulmonary baroreflex during exercise provides evidence for a role in mediating sympathetic nerve activity and blood pressure responses. In addition, recent investigations have demonstrated an interaction between cardiopulmonary baroreceptors and the arterial baroreflex during dynamic exercise, which contributes to the magnitude of exercise-induced increases in blood pressure as well as the resetting of the arterial baroreflex. Furthermore, neural inputs from the cardiopulmonary baroreceptors appear to play an important role in establishing the operating point of the arterial baroreflex. This symposium review highlights recent studies in these important areas indicating that the interactions of four neural mechanisms (central command, the exercise pressor reflex, the arterial baroreflex and cardiopulmonary baroreflex) are integral in mediating the neural cardiovascular adjustments to exercise.
[show abstract][hide abstract] ABSTRACT: Sympathetic vasoconstriction is normally attenuated in exercising muscle, but this functional sympatholysis is impaired in rats with hypertension or heart failure due to elevated levels of reactive oxygen species (ROS) in muscle. Whether ROS have a similar effect in the absence of cardiovascular disease or whether these findings extend to humans is not known. We therefore tested the hypothesis that chronic treatment with nitroglycerin (NTG) to induce nitrate tolerance, which is associated with excessive ROS production, impairs functional sympatholysis in healthy rats and humans. NTG treatment increased ethidium fluorescence in rat muscles and urinary F(2)-isoprostanes in humans, demonstrating oxidative stress. In vehicle-treated rats, sympathetic nerve stimulation (1 to 5 Hz) evoked decreases in femoral vascular conductance at rest (range, -30 to -63%) that were attenuated during hindlimb contraction (range, -2 to -31%; P < 0.05). In NTG-treated rats, vasoconstrictor responses were similar at rest, but were enhanced during contraction (range, -17 to -50%; P < 0.05 vs. vehicle). Infusion of the ROS scavenger tempol restored sympatholysis in these rats. In humans, reflex sympathetic activation during lower body negative pressure (LBNP) evoked decreases in muscle oxygenation in resting forearm (-12 ± 1%) that were attenuated during handgrip exercise (-3 ± 1%; P < 0.05). When these subjects became nitrate tolerant, LBNP-induced decreases in muscle oxygenation were unaffected at rest, but were enhanced during exercise (-9 ± 1%; P < 0.05 vs. before NTG). Collectively, these data indicate that functional sympatholysis is impaired in otherwise healthy nitrate-tolerant rats and humans by a mechanism probably involving muscle oxidative stress.
The Journal of Physiology 11/2011; 590(Pt 2):395-407. · 4.38 Impact Factor