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.
Okamura
T
T
Department of Pharmacology, School of Medicine, Shiga University of Medical Science, Ohtsu, Japan.
Toda
N
N
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D018738:Hexamethonium / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D019335:Nitroarginine; D011224:Prazosin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D019335:Nitroarginine; D014660:Vasoactive Intestinal Peptide; D018738:Hexamethonium; D009538:Nicotine; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D011224:Prazosin; D007213:Indomethacin