Biomedical subjects

L I Sinoway

Publications and source records attributed to L I Sinoway.

At least 37 records · Page 2Linked to original sources

PubMed1998

Systemic hypoxia elevates skeletal muscle interstitial adenosine levels in humans.

BACKGROUND: Adenosine is a potent vasodilator that has been shown to increase in cardiac tissue in response to hypoxia. However, peripheral vasodilatation also occurs during hypoxia, and the vasoactive substance(s) responsible for skeletal muscle vasodilation have not yet been completely identified. Therefore, the purpose of this study was to measure and quantify skeletal muscle interstitial adenosine during acute systemic hypoxia. METHODS AND RESULTS: Skeletal muscle interstitial adenosine concentrations were determined by the microdialysis technique, in which 4 semipermeable microdialysis probes were inserted into the vastus lateralis muscle of 6 healthy male subjects and perfused at a rate of 5 microL/min with Ringer's solution. Sixty minutes after the insertion of the microdialysis probes, systemic hypoxia was induced for 30 minutes by having the subjects breathe a mixture of 10.5% O2 in N2. Arterial oxygen saturation (fingertip oximeter) was lowered (P<0.05) from 96+/-0.7% to 74.9+/-1.4%, and forearm blood flow was increased 28%. During normoxia, the interstitial adenosine concentration was 0. 44+/-0.08 micromol/L, and it was increased to 1.03+/-0.15 (P<0.05) and 0.85+/-0.09 (P<0.05) after 15 and 30 minutes of hypoxia, respectively. CONCLUSIONS: These data are consistent with the concept that during acute systemic hypoxia, interstitial adenosine plays a key role in stimulating peripheral vasodilation.

Adenosine↗

PubMed1998

Fruit consumption, fitness, and cardiovascular health in female adolescents: the Penn State Young Women's Health Study.

The objective of this study was to compare the relations among nutrient intake, fitness, serum antioxidants, and cardiolipoprotein profiles in female adolescents. The study design was a cross-sectional analysis of the Penn State Young Women's Health Study. The present study was performed with the entire cohort (n = 86) when they were 17.1+/-0.5 y (x+/-SD) of age. Primary measurements included cardiolipoprotein indexes, serum antioxidants, nutrient intakes, aerobic fitness, and percentage body fat. The cohort was stratified by estimated maximal oxygen uptake (VO2max) measurements and by percentage body fat. The fifth quintile by estimated VO2max had significantly lower percentage body fat, higher athletic scores, higher fruit intake, lower total serum cholesterol, and lower ratios of total serum cholesterol to HDL cholesterol than members of the first quintile. When the members of the first and fifth quintiles by percentage body fat were compared, the first quintile had significantly lower weight, lower body mass index, higher estimated VO2max, higher athletic scores, lower ratios of total serum cholesterol to HDL cholesterol, and higher fruit, carbohydrate, and fiber intakes. Correlation analyses performed with the data for the entire cohort showed fruit consumption to be positively correlated with estimated VO2max, and predicted VO2max to be positively correlated with circulating beta-carotene and alpha-tocopherol. This study provided evidence that the positive associations of exercise and fruit consumption with cardiovascular health apply to female adolescents as well as to adults.

Adipose Tissue↗

PubMed1998

Forearm training reduces the exercise pressor reflex during ischemic rhythmic handgrip.

We examined the effects of unilateral, nondominant forearm training (4 wk) on blood pressure and forearm metabolites during ischemic and nonischemic rhythmic handgrip (30 1-s contractions/min at 25% maximal voluntary contraction). Contractions were performed by 10 subjects with the forearm enclosed in a pressurized Plexiglas tank to induce ischemic conditions. Training increased the endurance time in the nondominant arm by 102% (protocol 1). In protocol 2, tank pressure was increased in increments of 10 mmHg/min to +50 mmHg. Training raised the positive-pressure threshold necessary to engage the pressor response. In protocol 3, handgrip was performed at +50 mmHg and venous blood samples were analyzed. Training attenuated mean arterial pressure (109 +/- 5 and 98 +/- 4 mmHg pre- and posttraining, respectively, P < 0.01), venous lactate (2.9 +/- 0.4 and 1.8 +/- 0.3 mmol/l pre- and posttraining, respectively, P < 0.01), and the pH response (7.21 +/- 0.02 and 7.25 +/- 0.01, pre- and posttraining, respectively, P < 0.01). However, deep venous O2 saturation was unchanged. Training increased the positive-pressure threshold for metaboreceptor engagement, reduced metabolite concentrations, and reduced mean arterial pressure during ischemic exercise.

Adult↗

PubMed1998

Sympathetic discharge and vascular resistance after bed rest.

The effect of -6 degrees head-down-tilt bed rest (HDBR) for 14 days on supine sympathetic discharge and cardiovascular hemodynamics at rest was assessed. Mean arterial pressure, heart rate (n = 25), muscle sympathetic nerve activity (MSNA; n = 16) burst frequency, and forearm blood flow (n = 14) were measured, and forearm vascular resistance (FVR) was calculated. Stroke distance, our index of stroke volume, was derived from measurements of aortic mean blood velocity (Doppler) and R-R interval (n = 7). With these data, an index of total peripheral resistance was determined. Heart rate at rest was greater in the post (71 +/- 2 beats/min)- compared with the pre-HDBR test (66 +/- 2 beats/min; P < 0.003), but mean arterial pressure was unchanged. Aortic stroke distance during post-HDBR (15.5 +/- 1.1 cm/beat) was reduced from pre-HDBR levels (20.0 +/- 1.5 cm/beat) (P < 0.03). Also, MSNA burst frequency was reduced in the post (16.7 +/- 2.8 beats/min)- compared with the pre (25.2 +/- 2.6 beats/min)-HDBR condition (P < 0.01). Bed rest did not alter forearm blood flow, FVR, or total peripheral resistance. Thus reductions in MSNA with HDBR were not associated with a decrease in FVR.

Adaptation, Physiological↗

PubMed1998

Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure.

In congestive heart failure (CHF), the mechanisms of exercise-induced sympathoexcitation are poorly defined. We compared the responses of sympathetic nerve activity directed to muscle (MSNA) and to skin (SSNA, peroneal microneurography) during rhythmic handgrip (RHG) at 25% of maximal voluntary contraction and during posthandgrip circulatory arrest (PHG-CA) in CHF patients with those of an age-matched control group. During RHG, the CHF patients fatigued prematurely. At end exercise, the increase in MSNA was similar in both groups (CHF patients, n = 12; controls, n = 10). However, during PHG-CA, in the controls MSNA returned to baseline, whereas it remained elevated in CHF patients (P < 0.05). Similarly, at end exercise, the increase in SSNA was comparable in both groups (CHF patients, n = 11; controls, n = 12), whereas SSNA remained elevated during PHG-CA in CHF patients but not in the controls (P < 0.05). In a separate control group (n = 6), even high-intensity static handgrip was not accompanied by sustained elevation of SSNA during PHG-CA. 31P-nuclear magnetic resonance spectroscopy during RHG demonstrated significant muscle acidosis and accumulation of inorganic phosphate in CHF patients (n = 7) but not in controls (n = 9). We conclude that in CHF patients rhythmic forearm exercise leads to premature fatigue and accumulation of muscle metabolites. The prominent PHG-CA response of MSNA and SSNA in CHF patients suggests activation of the muscle metaboreflex. Because, in contrast to controls, in CHF patients both MSNA and SSNA appear to be under muscle metaboreflex control, the mechanisms and distribution of sympathetic outflow during exercise appear to be different from normal.

Adult↗

PubMed1998

Head-down-tilt bed rest alters forearm vasodilator and vasoconstrictor responses.

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.

Adult↗

PubMed1998

Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat.

We used the microdialysis technique to measure the interstitial concentration of several putative metabolic stimulants of the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 +/- 5 beats/min and 21 +/- 8 mmHg and 27 +/- 9 beats/min and 37 +/- 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned to baseline after 10 min of recovery. Interstitial lactate rose (P < 0. 05) by 0.41 +/- 0.15 and 0.56 +/- 0.16 mM for the 3- and 5-Hz stimulation protocols, respectively, and were not statistically different from one another. Interstitial lactate levels remained above (P < 0.05) baseline during recovery in the 5-Hz group. Dialysate phosphate concentrations (corrected for shifts in probe recovery) rose with stimulation (P < 0.05) by 0.19 +/- 0.08 and 0.11 +/- 0.03 mM for the 3- and 5-Hz protocols. There were no differences between groups. The resting dialysate K+ concentrations for the 3- and 5-Hz conditions were 4.0 +/- 0.1 and 3.9 +/- 0.1 meq/l, respectively. During stimulation the dialysate K+ concentrations rose steadily for both conditions, and the increase from rest to stimulation (P < 0.05) was 0.57 +/- 0.19 and 0.81 +/- 0.06 meq/l for the 3- and 5-Hz conditions, respectively, with no differences between groups. Resting dialysate pH was 6.915 +/- 0.055 and 6.981 +/- 0.032 and rose to 7.013 (P < 0.05) and 7.053 (P < 0.05) for the 3- and 5-Hz conditions, respectively, and then became acidotic (6. 905, P < 0.05) during recovery (5 Hz only). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These data suggest that interstitial K+ and phosphate, but not lactate and H+, may contribute to the stimulation of thin fiber muscle afferents during contraction.

Animals↗

PubMed1998

Maintained exercise pressor response in heart failure.

The impact of forearm blood flow limitation on muscle reflex (metaboreflex) activation during exercise was examined in 10 heart failure (HF) (NYHA class III and IV) and 9 control (Ctl) subjects. Rhythmic handgrip contractions (25% maximal voluntary contraction, 30 contractions/min) were performed over 5 min under conditions of ambient pressure or with +50 mmHg positive pressure about the exercising forearm. Mean arterial blood pressure (MAP) and venous effluent hemoglobin (Hb) O2 saturation, lactate and H+ concentrations ([La] and [H+], respectively) were measured at baseline and during exercise. For ambient contractions, the increase (Delta) in MAP by end exercise (DeltaMAP; i.e., the exercise pressor response) was the same in both groups (10.1 +/- 1.2 vs. 7.33 +/- 1.3 mmHg, HF vs. Ctl, respectively) despite larger Delta[La] and Delta[H+] for the HF group (P < 0.05). With ischemic exercise, the DeltaMAP for HF (21.7 +/- 2.7 mmHg) exceeded that of Ctl subjects (12.2 +/- 2.8 mmHg) (P < 0.0001). Also, for HF, Delta[La] (2.94 +/- 0.4 mmol) and Delta[H+] (24.8 +/- 2.7 nmol) in the ischemic trial were greater than in Ctl (1.63 +/- 0.4 mmol and 15.3 +/- 2.8 nmol; [La] and [H+], respectively) (P < 0.02). Hb O2 saturation was reduced in Ctl from approximately 43% in the ambient trial to approximately 27% with ischemia (P < 0.0001). O2 extraction was maximized under ambient exercise conditions for HF but not for Ctl. Despite progressive increases in blood perfusion pressure over the course of ischemic exercise, no improvement in Hb O2 saturation or muscle metabolism was observed in either group. These data suggest that muscle reflex activation of the pressor response is intact in HF subjects but the resulting improvement in perfusion pressure does not appear to enhance muscle oxidative metabolism or muscle blood flow, possibly because of associated increases in sympathetic vasoconstriction of active skeletal muscle.

Adult↗

PubMed1998

Effects of the ovarian cycle on sympathetic neural outflow during static exercise.

We compared reflex responses to static handgrip at 30% maximal voluntary contraction (MVC) in 10 women (mean age 24.1 +/- 1.7 yr) during two phases of their ovarian cycle: the menstrual phase (days 1-4) and the follicular phase (days 10-12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response to static exercise were greater during the menstrual compared with follicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase (75 +/- 5.5 vs. 116 +/- 9.6 pg/ml, days 1-4 vs. days 10-12; P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 +/- 1.3 vs. 28.2 +/- 1.5 kg, days 1-4 vs. days 10-12; P = 0.13). In a group of experiments with the use of 31P-NMR spectroscopy, no phase effect was observed for H+ and H2PO-4 concentrations (n = 5). During an ischemic rhythmic handgrip paradigm (20% MVC), a phase effect was not observed for MSNA or H+ or H2PO-4 concentrations, suggesting that blood flow was necessary for the expression of the cycle-related effect. The present studies suggest that, during static handgrip exercise, MSNA is increased during the menstrual compared with the follicular phase of the ovarian cycle.

Adult↗

PubMed1997

Effects of supplemental oxygen on forearm vasodilation in humans.

Supplemental O2 reduces cardiac output and raises systemic vascular resistance in congestive heart failure. In this study, 100% O2 was given to normal subjects and peak forearm flow was measured. In experiment 1, 100% O2 reduced blood flow and increased resistance after 10 min of forearm ischemia (flow 56.7 +/- 7.9 vs. 47.8 +/- 6.7 ml.min-1.100 ml-1; P < 0.02; vascular resistance 1.7 +/- 0.2 vs. 2.4 +/- 0.4 mmHg.min.100 ml.ml-1; P < 0.03). In experiment 2, lower body negative pressure (LBNP; -30 mmHg) and venous congestion (VC) simulated the high sympathetic tone and edema of congestive heart failure. Postischemic forearm flow and resistance were measured under four conditions: room air breathing (RA); LBNP+RA; RA+LBNP+VC; and 100% O2+LBNP+VC. LBNP and VC did not lower peak flow. However, O2 raised minimal resistance (2.3 +/- 0.4 RA; 2.8 +/- 0.5 O2+LBNP+VC, P < 0.04). When O2 alone (experiment 1) was compared with O2+LBNP+VC (experiment 2), no effect of LBNP+VC on peak flow or minimum resistance was noted, although the return rate of flow and resistance toward baseline was increased. O2 reduces peak forearm flow even in the presence of LBNP and VC.

Adult↗

PubMed1997

Augmented sympathetic tone alters muscle metabolism with exercise: lack of evidence for functional sympatholysis.

It is unclear whether sympathetic tone opposes dilator influences in exercising skeletal muscle. We examined high levels of sympathetic tone, evoked by lower body negative pressure (LBNP, -60 mmHg) on intramuscular pH and phosphocreatine (PCr) levels (31P-nuclear magnetic resonance spectroscopy) during graded rhythmic handgrip (30 contractions/min; approximately 17, 34, 52 and 69% maximal voluntary contraction). Exercise was performed with LBNP and without LBNP (Control). At the end of exercise, LBNP caused lower levels of muscle pH (6.59 +/- 0.09) compared with Control (6.78 +/- 0.05; P < 0.05). PCr recovery, an index of mitochondrial respiration, was less during the recovery phase of the LBNP trial. Exercise mean arterial pressure was not altered by LBNP. The protocols were repeated with measurements of forearm blood flow velocity and deep venous samples (active forearm) of hemoglobin (Hb) saturation, pH, and lactate. With LBNP, mean blood velocity was reduced at rest, during exercise, and during recovery compared with Control (P < 0.05). Also, venous Hb saturation and pH levels during exercise and recovery were lower with LBNP and lactate was higher compared with Control (P < 0.05). We conclude that LBNP enhanced sympathetic tone and reduced oxygen transport. At high workloads, there was a greater reliance on nonoxidative metabolism. In other words, sympatholysis did not occur.

Adult↗

PubMed1996

Observations on carotid sinus hypersensitivity from direct intraneural recordings of sympathetic nerve traffic.

In summary, we studied 4 patients with mixed-type CS hypersensitivity. We demonstrated that CS massage rapidly inhibits sympathetic nerve activity and decreases heart rate. Arterial pressure starts to decline abruptly with complete sympathetic withdrawal, but the nadir is delayed, suggesting that arterial dilation is not instantaneous. Arterial pressure rebounds slowly, suggesting a latency between the neural reflex and vascular compliance. Pacing had little effect on preventing hypotension in these patients. Our data support the concept that sympathetic withdrawal is responsible for the vasodilatory component seen with CS syncope.

Aged↗

PubMed1996

Hemodynamic effects of supplemental oxygen administration in congestive heart failure.

OBJECTIVES: This study sought to determine the hemodynamic effects of oxygen therapy in heart failure. BACKGROUND: High dose oxygen has detrimental hemodynamic effects in normal subjects, yet oxygen is a common therapy for heart failure. Whether oxygen alters hemodynamic variables in heart failure is unknown. METHODS: We studied 10 patients with New York Heart Association functional class III and IV congestive heart failure who inhaled room air and 100% oxygen for 20 min. Variables measured included cardiac output, stroke volume, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance, mean arterial pressure and heart rate. Graded oxygen concentrations were also studied (room air, 24%, 40% and 100% oxygen, respectively; n = 7). In five separate patients, muscle sympathetic nerve activity and ventilation were measured during 100% oxygen. RESULTS: The 100% oxygen reduced cardiac output (from 3.7 +/- 0.3 to 3.1 +/- 0.4 liters/min [mean +/- SE], p < 0.01) and stroke volume (from 46 +/- 4 to 38 +/- 5 ml/beat per min, p < 0.01) and increased pulmonary capillary wedge pressure (from 25 +/- 2 to 29 +/- 3 mm Hg, p < 0.05) and systemic vascular resistance (from 1,628 +/- 154 to 2,203 +/- 199 dynes.s/cm5, p < 0.01). Graded oxygen led to a progressive decline in cardiac output (one-way analysis of variance, p < 0.0001) and stroke volume (p < 0.017) and an increase in systemic vascular resistance (p < 0.005). The 100% oxygen did not alter sympathetic activity or ventilation. CONCLUSIONS: In heart failure, oxygen has a detrimental effect on cardiac output, stroke volume, pulmonary capillary wedge pressure and systemic vascular resistance. These changes are independent of sympathetic activity and ventilation.

Adult↗

PubMed1996

Neural responses to exercise in humans: implications for congestive heart failure.

1. During static handgrip exercise, muscle metaboreceptors are stimulated, evoking the 'exercise pressor reflex.' As part of this reflex, sympathetic discharge to skeletal muscle is increased. The muscle 'metaboreceptors' are thought to be free nerve endings of unmyelinated group IV nerve fibres. These receptors are stimulated by a number of metabolites, including lactic acid, H+, diprotonated phosphate, adenosine and the biproducts of prostaglandin synthesis. 2. During chronic, repetitive activity, muscle metabolite-sensitive afferents may be desensitized. We speculate that metaboreceptor desensitization also occurs in congestive heart failure (HF). Despite this desensitization, sympathoexcitatory responses to forearm exercise are preserved. This suggest that some other neural system aside from muscle metaboreceptors must be activated to a greater degree in HF. We speculate that in HF the activity of muscle mechanoreceptors is increased. Furthermore, we believe that limb congestion can increase the discharge of muscle mechanoreceptors, thereby evoking non-metaboreceptor-mediated increases in sympathetic discharge. Future studies in our laboratory will examine the role limb congestion and decongestion play in evoking muscle mechano-receptor-mediated sympathoexcitatory responses.

Animals↗

PubMed1996

Influences of gender on sympathetic nerve responses to static exercise.

We compared reflex responses to static handgrip at 30% maximal voluntary contraction (MVC) in 26 untrained men (mean age 35 +/- 3 yr) and 23 untrained women (mean age 39 +/- 4 yr). Women demonstrated attenuated increases in blood pressure and muscle sympathetic nerve activity (MSNA; by microneurography) compared with men. This difference was also observed during a period of posthandgrip circulatory arrest. 31P-nuclear magnetic resonance (NMR) spectroscopy studies demonstrated attenuations in the production of diprotonated phosphate and the development of cellular acidosis in women compared with men. Subjects also performed ischemic handgrip to fatigue. During this paradigm, MSNA responses were similar in the two groups, suggesting that freely perfused conditions are necessary for the full expression of the gender effect. Finally, we examined MSNA responses to adductor pollicus exercise in 7 men (26 +/- 1 yr) and 6 women (25 +/- 2 yr). MVC values and times to fatigue were similar in the two groups (MVC: men, 4.3 +/- 0.4 kg; women, 4.0 +/- 0.3 kg; not significant. Time to fatigue: men, 209 +/- 16 s; women, 287 +/- 50 s; not significant). At periods of end exercise and postexercise circulatory arrest, MSNA responses were attenuated in the women compared with the men. We conclude that, during nonischemic static exercise, sympathetic neural outflow is less in women compared with men. This response is due to an attenuated metaboreflex in women. Finally, on the basis of the adductor pollicus experiments, this effect appears independent of muscle mass, workload, and the level of training.

Acidosis↗

PubMed1996

Influence of treatment on muscle sympathetic nerve activity in sleep apnea.

Obstructive sleep apnea (OSA) is a common disorder associated with systemic hypertension, myocardial infarction, stroke, and premature death. Elevated sympathetic tone has been documented previously in OSA and may contribute to the cardiovascular risk. As OSA therapy appears to reduce mortality, we wondered if decreased apnea activity would attenuate the sympathetic hyperactivity of untreated patients. Muscle sympathetic nerve activity (MSNA) was measured during wakefulness via peroneal microneurography in seven patients with documented OSA before and at least 1 mo after compliance-monitored nasal continuous positive airway pressure (CPAP) therapy. Before institution of CPAP therapy, MSNA was high in all patients and decreased after CPAP therapy (baseline versus CPAP: 69.4 +/- 15.3 versus 53.9 +/- 10.5 bursts/min, mean +/- SD; p<0.01). However, the decrease in MSNA was limited to the four patients with the greatest nightly use of CPAP (> or = 4.5 h/night), whereas it remained unchanged in the three patients who were less compliant. There was a direct linear correlation between the decrease in MSNA (bursts/min) and the average hours of CPAP use per night (r = 0.87, p = 0.01). We conclude that in patients with OSA effective reduction in apnea activity with CPAP therapy diminishes the high sympathetic tone present during resting wakefulness.

Adult↗

PubMed1996

Smoking and idiopathic congestive cardiomyopathy.

Two case control studies were performed to evaluate whether smoking may affect myocardial function. Cardiomyopathy subjects had a greater pack year smoking history than 52 control subjects with no CAD (p < 0.02) and were more likely to have diabetes (p < 0.10), but they did not differ from controls with respect to age, alcohol intake, or the presence of hypertension. The risk of cardiomyopathy doubled with an increase of 39 pack years. Smoking history was not related to ejection for fraction for subjects with severe coronary artery disease. These results suggest that smoking may be an important risk factor for idiopathic congestive cardiomyopathy.

Adult↗

PubMed1994

Role of diprotonated phosphate in evoking muscle reflex responses in cats and humans.

Lactic acid and H+ evoke muscle reflexes that raise sympathetic nerve activity. Whether these substances are direct afferent stimulants or markers for the acidification of other substances is unknown. Diprotonated phosphate (H2PO4-), a possible mediator of fatigue, increases as the cell acidifies and phosphate is produced. Its role in evoking muscle reflexes is unknown. We used 31P-nuclear magnetic resonance to measure forearm muscle H+ and H2PO4- and microneurography to measure muscle sympathetic nerve activity (MSNA, peroneal nerve) during a handgrip protocol designed to dissociate H+ from H2PO4-. Ischemic handgrip (50% maximal voluntary contraction x 2 min) was followed by a 1-min rest period during which the muscle was freely perfused. This was followed by a second bout of ischemic handgrip and a 5-min recovery. In seven of eight subjects, MSNA correlated with H2PO4-, whereas it correlated with pH in only one subject. To determine whether muscle reflex responses are evoked by H+, lactic acid, monoprotonated phosphate (HPO4(2-), or H2PO4-, we injected H+, lactate, H2PO4- [all 50 mM in 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffered to pH 6], and HPO4(2-) (50 mM, pH 7.5 in 10 mM HEPES) into the arterial supply of the triceps surae of the cat (n = 9) as we measured mean arterial blood pressure (MAP). H2PO4- increased MAP more than HPO4(2-), H+, or lactate (27.1 +/- 3.7 vs. 5.0 +/- 1.3, 4.6 +/- 3.1, and 7.7 +/- 3.2 rise in mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗