Guanethidine evokes vasodilatation in guinea pig mesenteric artery by acting on sensory nerves.
In precontracted, endothelium-free guinea pig mesenteric artery rings, in which adrenergic vasoconstrictor responses had been eliminated, guanethidine (1-30 microM) produced a vasodilatation of 69.3+/-4.4%. The vasodilatation was reduced 89% by capsaicin (10 microM) or 55% by tetrodotoxin (10 microM), indicating mediation of this effect by primary sensory nerves. The nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (100 microM, 30 min) but not its stereoisomer reduced the guanethidine vasodilatation by 70%. Blockade of monoamine uptake with ouabain (25 microM, 15 min) or cocaine (5 microM, 5 min) reduced the guanethidine-induced vasodilatation by 85 and 67%, respectively. These results suggest that guanethidine produced vasodilatation by being transported into capsaicin-sensitive primary sensory nerves where it functioned as a substrate for nitric oxide synthase to generate a vasodilatory substance.
Zheng
Z L
ZL
Department of Physiology, Michigan State University, B-340 Life Sciences, East Lansing, MI 48824-1317, USA.
Shimamura
K
K
Anthony
T L
TL
Kreulen
D L
DL
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006145:Guanethidine / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D018663:Adrenergic Agents; D009569:Nitric Oxide; D002211:Capsaicin; D006145:Guanethidine