Mediators of contraction-evoked skeletal muscle depressor response in anesthetized rats

In the present study, mediators of muscle contraction-evoked cardiovascular responses were examined in anesthetized rats. Rhythmic contractions of the hindlimb triceps surae muscle were produced by stimulating the tibial nerve (motor threshold 22.7 +/- 2.3 microA; n = 10) by using a 1 s on-1 s off pattern. Mean arterial pressure (MAP) and heart rate (HR) responses were recorded before and after 1) muscarinic receptor blockade (atropine sulfate; 2.0 mg/kg i.v., n = 5); 2) nitric oxide synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME; 300 microM/kg i.v., n = 7); 3) beta-adrenoceptor blockade (propranolol; 2.0 mg/kg i.v., n = 10); and 4) bilateral adrenalectomy (n = 4). Rhythmic stimulation (10-s) significantly reduced MAP (P < 0.05) and elicited small decreases in HR that were abolished by neuromuscular blockade (n = 4). Atropine had no effect on MAP or HR responses to contraction. L-NAME increased baseline MAP (112.2 +/- 2.2 to 137.1 +/- 4.6 mmHg, P < 0.05) and attenuated contraction-evoked reductions of MAP (P < 0.05) without affecting HR. L-NAME-induced response deficits were mimicked in four separate rats by elevating MAP with phenylephrine (7-10 micrograms.kg-1.h-1 iv) to a level not different from that produced by L-NAME. Bilateral adrenalectomy and propranolol did not significantly affect HR responses but reduced contraction-evoked decreases in MAP from 14.3 +/- 2.9 to 7.7 +/- 2.2 mmHg and from 13.4 +/- 1.3 to 6.3 +/- 3.1 mmHg, respectively (P < 0.05). Baseline MAP was unchanged. We conclude that adrenal catecholamines, acting at beta-adrenoceptors, contribute significantly to the contraction-evoked depressor response in rats. No role for muscarinic receptors is evident in this response. Furthermore, attenuation of depressor responses to contraction after nitric oxide inhibition could result from an indirect effect of the pressor actions of L-NAME.