N omega-nitro-L-arginine inhibits vasodilations and elevations of both cyclic AMP and cyclic GMP levels in rat aorta induced by calcitonin gene-related peptide (CGRP).
Our previous studies showed that vasodilations and elevations of both cyclic AMP and cyclic GMP levels in rat aorta induced by rat calcitonin gene-related peptide (rCGRP) are inhibited by hemoglobin and methylene blue, blockers of the endothelium-derived relaxant factor (EDRF, now recognized as nitric oxide [NO]). In the present study, we used N omega-nitro-L-arginine (L-NNA), a selective inhibitor of nitric oxide synthase, to test whether rCGRP-induced relaxations and cyclic AMP and cyclic GMP responses in rat aorta require de novo synthesis of NO. L-NNA (30 microM, 15 min) inhibited by 84, 76 and 73% the relaxations induced by rCGRP at 1, 10 and 100 nM, respectively. D-NNA (30 microM), which does not inhibit nitric oxide synthase, did not block rCGRP-induced vasorelaxations. Addition of L-arginine (3 mM) 5 min before L-NNA completely prevented the L-NNA-inhibition of CGRP-induced relaxations. L-NNA (30 microM, 15 min) also inhibited the elevations of both cyclic AMP and cyclic GMP levels caused by CGRP (100 nM). The data suggest that de novo synthesis of nitric oxide from its precursor L-arginine is required for rCGRP to induce vasodilations and elevations of both cyclic AMP and cyclic GMP levels in rat aorta.
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Department of Physiology and Biophysics, Stroke Program Center of Excellence of Sanders-Brown Research Center on Aging, University of Kentucky College of Medicine, Lexington 40536-0230.
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D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide