NITRIC-OXIDE IS A MEDIATOR OF TACHYKININ NK3 RECEPTOR-INDUCED RELAXATION IN RAT MESENTERIC-ARTERY

1 The mechanism of vasodilatation induced by tachykinin peptides was studied in isolated mesenteric arteries of rats. 2 Senktide, a selective NK3 agonist, elicited potent endothelium-dependent relaxation of arteries precontracted with phenylephrine (10(-5)M), but an NK1 agonist did not. 3 A non-peptide NK3 antagonist, SR 142801, inhibited senktide-induced relaxation. However, a non-peptide NK1 antagonist, CP-96,345, and a peptide-based NK2 antagonist, L-659,877, had no effect on senktide-induced relaxation. 4 N-omega-nitro-L-arginine (L-NOARG), a nitric oxide synthesis inhibitor, markedly attenuated the relaxant response to senktide. 5 These results suggest that the endothelium of rat mesenteric arteries possesses tachykinin NK3 receptors, and that NK3 agonist-induced vasodilatation is mediated by release of nitric oxide (NO) from the endothelium.