Mechanism underlying nicotine-induced relaxation in dog saphenous arteries.

In isolated dog saphenous arterial strips denuded of the endothelium, the mechanism underlying relaxations induced by nicotine was analyzed. Nicotine-induced contractions were abolished by treatment with prazosin and alpha,beta-methylene ATP. In the strips thus treated and contracted with prostaglandin F2 alpha, nicotine produced a relaxation, which was abolished by hexamethonium. The relaxation was inhibited by cyclooxygenase inhibitors and markedly attenuated in the strips made tachyphylactic to calcitonin-gene related peptide (CGRP) but not to vasoactive intestinal polypeptide. The remaining relaxation in the strips treated with indomethacin and CGRP was abolished by NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, and the inhibition was reversed by L-arginine but not by D-arginine. Perivascular nerves containing NO synthase immunoreactivity have been demonstrated in an earlier report. CGRP-immunoreactive nerve fibers were observed in the adventitia. It appears that the nicotine-induced relaxation is associated with stimulation of vasodilator nerves liberating NO and CGRP, and adrenergic neurogenic vasoconstriction predominates over the neurogenic vasodilatation in dog saphenous arteries.