Sympathetic vasoconstriction is attenuated by nitric oxide in contracting rat hindlimb

Sympathetic vasoconstriction is greatly attenuated by metabolic events in contracting skeletal muscle both in conscious humans and anesthetized rats (JCI 98:584, 1996; AJP 266:H920, 1994), but the underlying mechanism is not well defined. The aim of this study was to determine whether the contraction-induced attenuation of sympathetic vasoconstriction is mediated by nitric oxide, adenosine, or prostacyclin, all of which have been implicated in the metabolic regulation of muscle blood flow. We measured arterial pressure and femoral artery blood flow velocity responses to lumbar sympathetic nerve stimulation in 3 groups of chloralose-anesthetized rats (n=5 each) at rest and during intermittent, tetanic hindlimb contractions before and after: a) nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester (L-NAME; 5 mg/kg, ia); b) adenosine receptor blockade with 8-(p-sulfophenyl)-theophylline (8-PST; 10 mg/kg, iv); and c) cyclooxygenase inhibition with indomethacin (INDO; 5 mg/kg, iv). The changes in femoral vascular conductance elicited by sympathetic nerve stimulation in resting and contracting hindlimb are shown in the table below (*p<0.05 vs. Before). L-NAME 8-PST INDO Before After Before After Before After Rest -61±3% -69±3% -73±2% -70±3% -60±2% -59±4% Contraction -10±5% -37±8%* -11±4% +3±7% -10±1% -9±3% These data suggest that the production of nitric oxide, but not adenosine or prostacyclin, is an important mechanism underlying contraction-induced attenuation of sympathetic vasoconstriction in rat hindlimb.