We used phosphorus nuclear magnetic resonance spectroscopy (31P-NMR) to probe the cellular events in contracting muscle that initiate the reflex stimulation of sympathetic outflow during exercise. In conscious humans, we performed 3"P-NMR on exercising forearm muscle and simultaneously recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve to determine if the activation of MSNA is coupled to muscle pH, an index of glycolysis, or to the concentrations (0) of inorganic phosphate (Pi) and adenosine diphosphate (ADP) which are modulators of mitochondrial respiration. During both static and rhythmic handgrip, the onset of sympathetic activation in resting muscle coincided with the development of cellular acidification in active muscle. Furthermore, increases in MSNA were correlated closely with decreases in intracellular pH but dissociated from changes in phosphocreatine (IPCrI), [Pi], and [ADPI. The principal new conclusion is that activation of muscle sympathetic outflow during exercise in humans is coupled to the cellular accumulation of protons in contracting muscle.

We used intraneural recordings of sympathetic nerve activity in conscious humans to determine if central command increases sympathetic discharge to resting skeletal muscle during static exercise. In nine healthy subjects, we measured arterial pressure, heart rate, and muscle sympathetic nerve activity with microelectrodes in the peroneal nerve of the resting leg during 1) static handgrip at 15% and 30% maximal voluntary contraction and 2) attempted handgrip during partial neuromuscular blockade produced by systemic administration of tubocurarine chloride (0.075 mg/kg i.v.). During curare, subjects reported that they used near-maximal motor effort to attempt a sustained handgrip contraction, but they generated almost no force. Without sustained contraction, the intent to exercise alone, that is, central command, caused statistically significant (p less than 0.05) increases in muscle sympathetic nerve activity as well as in arterial pressure and heart rate. However, the increases in muscle sympathetic nerve activity (+ 56 +/- 16% over control) and in mean arterial pressure (+ 12 +/- 2 mm Hg) during attempted handgrip were much smaller (p less than 0.05) than the sympathetic nerve response (+ 217 +/- 37% over control) and pressor response (+ 25 +/- 3 mm Hg) during an actual static handgrip at 30% maximal voluntary contraction. In contrast, heart rate increased as much during the attempted contraction (+ 18 +/- 2 beats/min) as during the actual contraction at 30% maximal voluntary contraction (+ 16 +/- 4 beats/min). In 11 additional subjects, the heart rate responses during curare were greatly attenuated (p less than 0.05) by atropine but were not significantly affected by propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Static muscle contraction activates metabolically sensitive muscle afferents that reflexively increase sympathetic nerve activity and arterial pressure. To determine if this contractioninduced reflex is modulated by the sinoaortic baroreflex, we performed microelectrode recordings of sympathetic nerve activity to resting leg muscle during static handgrip in humans while attempting to clamp the level of baroreflex stimulation by controlling the exercise-induced rise in blood pressure with pharmacologic agents. The principal new finding is that partial pharmacologic suppression of the rise in blood pressure during static handgrip (nitroprusside infusion) augmented the exercise-induced increases in heart rate and sympathetic activity by > 300%. Pharmacologic accentuation of the exercise-induced rise in blood pressure (phenylephrine infusion) attenuated these reflex increases by > 50%. In contrast, these pharmacologic manipulations in arterial pressure had little or no effect on: (a) forearm muscle cell pH, an index of the metabolic stimulus to skeletal muscle afferents; or (b) central venous pressure, an index of the mechanical stimulus to cardiopulmonary afferents.We conclude that in humans the sinoaortic baroreflex is much more effective than previously thought in buffering the reflex sympathetic activation caused by static muscle contraction. (J.

Static muscular contraction in anesthetized animals has been firmly established to reflexly increase arterial pressure. Although group III and IV muscle afferents are known to be responsible for this reflex pressor response, there is no evidence that the stimulation of muscle mechanoreceptors, many of which are supplied by group III fibers, plays a role in causing this contraction-induced reflex effect. To provide this evidence, we recorded renal sympathetic nerve activity in chloralose-anesthetized cats while contracting the triceps surae muscles. We found that static contraction tripled renal nerve activity within three seconds of its onset, an increase that was abolished by cutting the L6 and S2 dorsal roots. On average, the contraction-induced increase in renal nerve activity was observed 0.8 +/- 0.1 seconds after the onset of this maneuver. In addition, intermittent tetanic contractions synchronized renal nerve discharge so that a burst of activity was evoked by each contraction. A similarly synchronized renal nerve discharge was evoked in paralyzed cats by electrical stimulation of the tibial nerve at five times motor threshold, a current intensity that activates group III afferents. We conclude that, in anesthetized animal preparations, mechanoreceptors with group III afferents contribute to the reflex stimulation of renal sympathetic outflow evoked by muscular contraction.