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 NG-nitro-L-arginine methyl ester (L-NAME, 25 mumol/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 micrograms/kg i.v.) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Davisson
R L
RL
Department of Pharmacology, University of Iowa, Iowa City 52242.
Johnson
A K
AK
Lewis
S J
SJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001808:Blood Vessels / Q000201:enzymology; D001949:Bretylium Compounds / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009574:Nitro Compounds / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013312:Stress, Physiological / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D001949:Bretylium Compounds; D009574:Nitro Compounds; D009603:Nitroso Compounds; D009599:Nitroprusside; D001120:Arginine; D009252:NADPH Dehydrogenase; C045166:bretylium; D019331:NG-Nitroarginine Methyl Ester