NITROSYL FACTORS MEDIATE ACTIVE NEUROGENIC HINDQUARTER VASODILATION IN THE CONSCIOUS RAT

Exposure to noxious environmental stimuli such as air-jet stress (AJS) produces a pattern of hemodynamic changes referred to as the ''defense reaction.'' In the rat these changes include a relatively modest increase in mean arterial blood pressure (MAP), tachycardia, renal and mesenteric vasoconstriction, and a marked hindquarter vasodilation. The aim of the present study was to determine whether the AJS-induced decrease in hindquarter resistance is mediated by a sympathetic neurogenic vasodilator system that uses nitric oxide (NO) and/or related nitrosyl factors. AJS produced a small, rapid increase in MAP, which quickly returned to baseline (within 5 seconds), and a substantial increase in hindquarter blood flow and decrease in hindquarter resistance, which occurred almost instantaneously (1 to 2 seconds) and were sustained for at least 30 seconds. The intravenous injection of either bretylium (5 mg/kg), which prevents impulse propagation-mediated release of neurotransmitters/neuromodulators from sympathetic terminals, or N-G-nitro-L-arginine methyl ester (L-NAME, 25 mu mol/kg), which blocks NO synthesis, essentially abolished the AJS-induced increase in hindquarter blood flow and fall in hindquarter resistance. In contrast, the hindquarter vasodilation produced by the NO donor sodium nitroprusside (4 mu g/kg IV) was markedly exaggerated in the bretylium- or L-NAME-treated rats. We also found that rat lumbar sympathetic fibers projecting to the hindquarter vasculature contain NADPH diaphorase, a marker for NO synthase in paraformaldehyde-perfused tissue. The above findings demonstrate that AJS produces a rapid and sustained increase in hindquarter blood flow, which is independent of changes in MAP, and suggest that these effects are mediated by active sympathetic neurogenic vasodilation involving the release of nitrosyl factors from postganglionic sympathetic neurons and/or the vascular endothelium.