Guanethidine evokes vasodilatation in guinea pig mesenteric artery by acting on sensory nerves

Abstract

In precontracted, endothelium-free guinea pig mesenteric artery rings, in which adrenergic vasoconstrictor responses had been eliminated, guanethidine (1–30 μM) produced a vasodilatation of 69.3±4.4%. The vasodilatation was reduced 89% by capsaicin (10 μM) or 55% by tetrodotoxin (10 μM), indicating mediation of this effect by primary sensory nerves. The nitric oxide synthase inhibitor N ω-nitro- l-arginine (100 μM, 30 min) but not its stereoisomer reduced the guanethidine vasodilatation by 70%. Blockade of monoamine uptake with ouabain (25 μM, 15 min) or cocaine (5 μM, 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.