Limb vascular conductance responses to pharmacological and nonexercise vasodilator stimuli are generally augmented in women compared with men. In the present investigation, we tested the hypothesis that exercise-induced vasodilator responses are also greater in women than men. Sixteen women and 15 men (20-30 yr) with similar fitness and activity levels performed graded quadriceps exercise (supine, single-leg knee extensions, 40 contractions/min) to maximal exertion. Active limb hemodynamics (left common femoral artery diameter and volumetric blood flow), heart rate (ECG), and beat-to-beat mean arterial blood pressure (MAP; radial artery tonometry) were measured during each 3-min workload (4.8 and 8 W/stage for women and men, respectively). The hyperemic response to exercise (slope of femoral blood flow vs. workload) was greater (P < 0.01) in women as was femoral blood flow at workloads >15 W. The leg vasodilatory response to exercise (slope of calculated femoral vascular conductance vs. absolute workload) was also greater in women than in men (P < 0.01) because of the sex difference in hyperemia and the women's lower MAP ( approximately 10-15 mmHg) at all workloads (P < 0.05). The femoral artery dilated to a significantly greater extent in the women ( approximately 0.5 mm) than in the men ( approximately 0.1 mm) across all submaximal workloads. At maximal exertion, femoral vascular conductance was lower in the men (men, 18.0 +/- 0.6 ml.min(-1)xmmHg(-1); women, 22.6 +/- 1.4 mlxmin(-1)xmmHg(-1); P < 0.01). Collectively, these findings suggest that the vasodilatory response to dynamic leg exercise is greater in young women vs. men.

Background-Blood flow limitation to exercising muscles engages the muscle reflex during exercise, evoking an increase in heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA). Methods and Results-In the current study, we examined forearm flow and autonomic responses to ischemic handgrip in young and older subjects. We studied 6 younger subjects (mean age 23.5Ϯ2.2 years) and 7 older subjects (mean age 65.0Ϯ2.4 years). Subjects performed rhythmic handgrip (thirty 1-sec contractions/min) at 30% maximal voluntary contraction during six 1-minute stages: freely perfused exercise (E1) and exercise with forearm pressure of ϩ10, ϩ20, ϩ30, ϩ40, and ϩ50 mm Hg (E2 through E6). We measured HR, BP, MSNA, forearm flow velocity, forearm venous oxygen saturation, H ϩ , and lactate. Compared with E1, ischemic exercise (E2 through E6) increased HR, BP, and MSNA, reduced forearm velocity, lowered venous oxygen saturation, and raised venous lactate and H ϩ . Compared with the younger subjects, the older subjects had attenuated BP at E6, attenuated MSNA indices (%⌬bursts, bursts/100 heart beats and signal averaged MSNA), attenuated H ϩ at E6, a trend toward higher levels of oxygen saturation, and similar forearm velocity and HR responses. Key Words: aging Ⅲ exercise Ⅲ reflex Ⅲ blood flow D uring exercise, the sympathetic nervous system is activated. This helps redistribute blood flow to active muscle and aids in preventing blood pressure (BP) from falling. 1 Two neural systems contribute to sympathetic activation: central command, 2 a feed-forward process, and a muscle reflex termed the exercise pressor reflex. 3 The muscle reflex is engaged when mechanically or metabolically sensitive thin fiber afferents within contracting muscle increase their discharge. 4 During forearm exercise, the muscle reflex is engaged when the muscle fatigues and/or when a mismatch occurs between blood supply and metabolic demand. 5 In the present study, we examined the effects of aging on the exercise pressor reflex in humans. Despite the fact that this reflex is an important determinant of exercise flow regulation, little is known about the effects of aging on this reflex. The reflex is evoked by a muscle work/blood flow mismatch. Therefore, to engage the reflex, a paradigm was employed in which the level of work was kept constant as external impedance to muscle flow was progressively increased. We examined whether age affects the BP response to reflex engagement and if sympathetic nerve responses to reflex engagement is different in young and older subjects. The results of these studies support the concept that the muscle reflex becomes attenuated with age. Conclusions-Aging Methods SubjectsSix young (4 males, 2 females; mean age 23.5 years; mean body mass index 23.5) and 7 older subjects (4 males, 3 females; mean age 65.0; body mass index 26.2) were studied. All were normotensive non-smokers on no medications. Each signed an Institutional Review Board-approved consent. Forearm PressureSubjects performed handgrip in a sealed...

We examined muscle sympathetic nerve activity (MSNA) in the nonexercising lower limb during repetitive static quadriceps contraction paradigm at 25% maximal voluntary contraction in eight men. Subjects performed 20-s contractions with 5-s rest periods for up to 12 contractions. Although the workload was constant, we found that MSNA amplitude rose as a function of contraction number [0.6 ln (amplitude/min)/contraction]; this suggests chemical sensitization of the muscle reflex response. We employed signal-averaging techniques and then integrated the data to examine the onset latency of the MSNA response as a function of the 25-s contraction-rest period. We observed an onset latency of approximately 4-6 s. Moreover, although the onset latency did not appear to vary as a function of contraction number, the rate of MSNA increase took approximately four contractions to reach a steady-state rate of rise; this suggests contraction-induced sensitization. The onset latency reported here is similar to findings in recent animal studies, but it is at odds with latencies determined in prior human handgrip contraction studies. We believe our data suggest that 1) mechanically sensitive afferents contribute importantly to the MSNA response to the paradigm employed and 2) these afferents may be sensitized by the chemical products of muscle contraction.

Obstructive apnea and voluntary breath holding are associated with transient increases in muscle sympathetic nerve activity (MSNA) and arterial pressure. The contribution of changes in blood flow relative to the contribution of changes in vascular resistance to the apnea-induced transient rise in arterial pressure is unclear. We measured heart rate, mean arterial blood pressure (MAP), MSNA (peroneal microneurography), and femoral artery blood velocity (V(FA), Doppler) in humans during voluntary end-expiratory apnea while they were exposed to room air, hypoxia (10.5% inspiratory fraction of O2), and hyperoxia (100% inspiratory fraction of O2). Changes from baseline of leg blood flow (Q) and vascular resistance (R) were estimated from the following relationships: Q proportional to V(FA), corrected for the heart rate, and R proportional to MAP/Q. During apnea, MSNA rose; this rise in MSNA was followed by a rise in MAP, which peaked a few seconds after resumption of breathing. Responses of MSNA and MAP to apnea were greatest during hypoxia and smallest during hyperoxia (P < 0.05 for both compared with room air breathing). Similarly, apnea was associated with a decrease in Q and an increase in R. The decrease in Q was greatest during hypoxia and smallest during hyperoxia (-25 +/- 3 vs. -6 +/- 4%, P < 0.05), and the increase in R was the greatest during hypoxia and the least during hyperoxia (60 +/- 8 vs. 21 +/- 6%, P < 0.05). Thus voluntary apnea is associated with vasoconstriction, which is in part mediated by the sympathetic nervous system. Because apnea-induced vasoconstriction is most intense during hypoxia and attenuated during hyperoxia, it appears to depend at least in part on stimulation of arterial chemoreceptors.

In humans, hypoxia leads to increased sympathetic neural outflow to skeletal muscle. However, blood flow increases in the forearm. The mechanism of hypoxia-induced vasodilation is unknown. To test whether hypoxia-induced vasodilation is cholinergically mediated or is due to local release of adenosine, normal subjects were studied before and during acute hypoxia (inspired O(2) 10.5%; approximately 20 min). In experiment I, aminophylline (50-200 microg. min(-1). 100 ml forearm tissue(-1)) was infused into the brachial artery to block adenosine receptors (n = 9). In experiment II, cholinergic vasodilation was blocked by atropine (0.4 mg over 4 min) infused into the brachial artery (n = 8). The responses of forearm blood flow (plethysmography) and forearm vascular resistance to hypoxia in the infused and opposite (control) forearms were compared. During hypoxia (arterial O(2) saturation 77 +/- 2%), minute ventilation and heart rate increased while arterial pressure remained unchanged; forearm blood flow rose by 35 +/- 6% in the control forearm but only by 5 +/- 8% in the aminophylline-treated forearm (P < 0.02). Accordingly, forearm vascular resistance decreased by 29 +/- 5% in the control forearm but only by 9 +/- 6% in the aminophylline-treated forearm (P < 0.02). Atropine did not attenuate forearm vasodilation during hypoxia. These data suggest that adenosine contributes to hypoxia-induced vasodilation, whereas cholinergic vasodilation does not play a role.

A Doppler signal converter has been developed to facilitate cardiovascular and exercise physiology research. This device directly converts audio signals from a clinical Doppler ultrasound imaging system into a real-time analog signal that accurately represents blood flow velocity and is easily recorded by any standard data acquisition system. This real-time flow velocity signal, when simultaneously recorded with other physiological signals of interest, permits the observation of transient flow response to experimental interventions in a manner not possible when using standard Doppler imaging devices. This converted flow velocity signal also permits a more robust and less subjective analysis of data in a fraction of the time required by previous analytic methods. This signal converter provides this capability inexpensively and requires no modification of either the imaging or data acquisition system.

To test the hypothesis that head-down-tilt bed rest (HDBR) for 14 days alters vascular reactivity to vasodilatory and vasoconstrictor stimuli, the reactive hyperemic forearm blood flow (RHBF, measured by venous occlusion plethysmography) and mean arterial pressure (MAP, measured by Finapres) responses after 10 min of circulatory arrest were measured in a control trial (n = 20) and when sympathetic discharge was increased by a cold pressor test (RHBF + cold pressor test; n = 10). Vascular conductance (VC) was calculated (VC = RHBF/MAP). In the control trial, peak RHBF at 5 s after circulatory arrest (34.1 +/- 2.5 vs. 48.9 +/- 4.3 ml . 100 ml-1 . min-1) and VC (0.34 +/- 0.02 vs. 0.53 +/- 0.05 ml . 100 ml-1 . min-1 . mmHg-1) were reduced in the post- compared with the pre-HDBR tests (P < 0. 05). Total excess RHBF over 3 min was diminished in the post- compared with the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). The ability of the cold pressor test to lower forearm blood flow was less in the post- than in the pre-HDBR test (P < 0.05), despite similar increases in MAP. These data suggest that regulation of vascular dilation and the interaction between dilatory and constrictor influences were altered with bed rest.

Muller MD, Gao Z, Drew RC, Herr MD, Leuenberger UA, Sinoway LI. Effect of cold air inhalation and isometric exercise on coronary blood flow and myocardial function in humans. J Appl Physiol 111: 1694 -1702, 2011. First published September 22, 2011 doi:10.1152/japplphysiol.00909.2011.-The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold ϩ grip protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial function (tissue Doppler imaging), O2 saturation, and pulmonary function were measured. The rate-pressure product (RPP) was used as an index of myocardial O2 demand, whereas CBV was used as an index of myocardial O2 supply. Compared with the sham protocol, the cold air protocol caused a significantly higher RPP, but there was a significant reduction in CBV. The cold ϩ grip protocol caused a significantly greater increase in RPP compared with the grip protocol (P ϭ 0.045), but the increase in CBV was significantly less (P ϭ 0.039). However, myocardial function was not impaired during the cold ϩ grip protocol relative to the grip protocol alone. Collectively, these data indicate that there is a supply-demand mismatch in the coronary vascular bed when cold ambient air is breathed during acute exertion but myocardial function is preserved, suggesting an adequate redistribution of blood flow. blood pressure; sympathetic nervous system; oxygen consumption; handgrip EXPOSURE TO COLD TEMPERATURES causes many physiological adjustments, most of which help prevent a fall in core body temperature. Specifically, peripheral vasoconstriction and shivering both raise blood pressure and effectively increase the work of the heart. These are known triggers of angina in clinical populations (33). Cardiac death is highest in the winter months, even in people who spend little time outdoors (45,54). While the effects of lowered skin temperature on cardiovascular function have been extensively studied (10,29,59,60), other mechanisms likely play a role in this process.Physical perturbation of the oropharynx and larynx elevates blood pressure in clinical settings (18,34), and laryngeal cold receptors have been identified in animals (38, 51). Previous studies (26,28,35,37) have shown that blood pressure, heart rate, and/or muscle sympathetic nerve activity are increased with cold air breathing in healthy humans. Acu...