Static muscular contraction has been firmly established to reflexly increase cardiovascular and ventilatory function. Although group III and IV fibers with endings in muscle have been shown to comprise the afferent arm of this reflex arc, little is known about the nature of the contraction-induced stimulus causing the activation of these fibers. This stimulus has often been suggested to be a metabolic product of muscular contraction. We have therefore recorded the impulse activity of group III and IV afferents with endings in the triceps surae muscles of barbiturate-anesthetized cats while we injected into the femoral artery substances believed to be metabolic products of muscular contraction. We found that lithium and sodium lactate (400 mM; 1 ml) had little or no effect on the discharge of group III and IV afferents. Likewise, monobasic sodium phosphate (20 and 400 mM; 1 ml) and 2-chloroadenosine (50-100 micrograms) had only trivial effects on the discharge of these afferents. By contrast, lactic acid (25 and 400 mM; 1 ml) and arachidonic acid (0.5-2.0 mg) caused significant increases in the activity of group III and IV afferents. Most of the excitatory effect of arachidonic acid on the discharge of the afferents was prevented by indomethacin, a cyclooxygenase inhibitor. We conclude that of the substances tested in our experiments, lactic acid and some cyclooxygenase products, such as prostaglandins and thromboxanes, are the most likely to be responsible for any metabolic stimulation of group III and IV afferents during muscular contraction.

The afferent arm of the reflex are responsible for the pressor response to static contraction is comprised of group III and IV fibers. The nature of the contraction-induced stimulus activating these fibers remains unclear. Evidence suggests that most group III afferents are sensitive to mechanical stimuli, whereas most group IV afferents are sensitive to metabolic stimuli. Recently, in anesthetized cats, stimulation of group III mechanoreceptors has been shown to have a role in the reflex pressor response to static contraction. In skin, the sensitivity of thin fiber mechanoreceptors to distortion of their receptive fields has been shown to be increased by both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. Therefore, in barbiturate-anesthetized cats we recorded the responses of group III muscle afferents to static contraction before and after arachidonic acid (1-2 mg ia) and/or indomethacin (5 mg/kg iv). Arachidonic acid increased the responses of group III afferents (n = 11) to contraction by 265% (from 0.17 +/- 0.07 to 0.62 +/- 0.24 impulses/s; P less than 0.025). Indomethacin decreased the responses of group III afferents (n = 9) to contraction by 61% (from 1.00 +/- 0.37 to 0.39 +/- 0.16 impulses/s; P less than 0.025). Arachidonic acid given after indomethacin increased the responses of two of four group III afferents to contraction. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism sensitize group III muscle afferents to static contraction.

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.

Static exercise increases arterial pressure, heart rate, and ventilation, effects which are believed in part to arise reflexly from a metabolic stimulus in the working muscle. In anesthetized cats, we tested the hypothesis that intra-arterial injections of lactic and hydrochloric acid, which created levels of these substances in muscle similar to those seen during contraction, reflexly increased cardiovascular and ventilatory function. Hydrochloric acid (32 and 57 mM; 1 ml) injected into the arterial supply of the triceps surae decreased intramuscular pH from 7.26 +/- 0.05 to 7.17 +/- 0.05 (P less than 0.01) and reflexly increased arterial pressure (23 +/- 7 mmHg; P less than 0.01), heart rate (11 +/- 2 beats/min; P less than 0.001), and ventilation (187 +/- 72 ml/min; P less than 0.05). Static contraction of the triceps surae decreased intramuscular pH from 7.28 +/- 0.06 to 7.13 +/- 0.06 (P less than 0.01). Lactic acid was more potent in causing reflexes than was equimolar HCl. For example, lactic acid containing 4 mM lactate and 0.87 mM H+ reflexly increased arterial pressure, heart rate, and ventilation, whereas 0.87 mM HCl did not. Intra-arterial sodium lactate (13 and 33 mM) at a neutral pH had no effect on these variables. We conclude that contraction-induced accumulation of H+, especially that arising from lactic acid, might provide a metabolic stimulus to evoke reflex autonomic effects.

Cyclooxygenase products of arachidonic acid might be some of the substances that accumulate in contracting muscle to cause the reflex increases in arterial pressure and ventilation that are evoked by exercise. Recently, cyclooxygenase blockade has been shown to attenuate the reflex cardiovascular responses to static muscular contraction in anesthetized cats. Group IV afferents are believed to comprise part of the afferent arm of the reflex arc, the activation by which static muscular contraction causes these cardiovascular effects. We therefore examined the effects of indomethacin and aspirin, two cyclooxygenase-blocking agents, on the responses to static contraction of group IV afferents with endings in the triceps surae muscles of anesthetized cats. We found that indomethacin (5 mg/kg iv) decreased the responses to contraction of each of eight group IV afferents tested. Likewise, aspirin (50 mg/kg iv) decreased the responses to contraction of each of four group IV afferents tested. On the other hand, we found that arachidonic acid (2 mg) injected into the femoral artery did not increase the responses to contraction of four group IV afferents that were stimulated by this maneuver. In addition, arachidonic acid injection did not cause any of seven group IV afferents not stimulated by static contraction to become responsive to this maneuver. Nevertheless, arachidonic acid injection with the muscle at rest stimulated five of seven contraction-insensitive and two of four contraction-sensitive group IV afferents. Our data suggest that cyclooxygenase metabolites of arachidonic acid are needed for the full expression of the responses of group IV muscle afferents to static contraction.(ABSTRACT TRUNCATED AT 250 WORDS)