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 mu M) produced a vasodilatation of 69.3 +/- 4.4%. The vasodilatation was reduced 89% by capsaicin (10 mu M) or 55% by tetrodotoxin (10 mu M), indicating mediation of th is effect by primary sensory nerves. The nitric oxide synthase inhibitor N-omega-nitro-L-arginine (100 mu M, 30 min) but not its stereoisomer reduced the guanethidine vasodilatation by 70%. Blockade of monoamine uptake with ouabain (25 mu M, 15 min) or cocaine (5 mu M, 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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.