Abstract
Nitroglycerin dose-response curves were performed on phenylephrine-contracted helical strips from canine dorsal pedal arteries and medial saphenous veins. A 50-fold difference was observed in the threshold dose required for relaxation in the saphenous vein (1 x 10-9 M) and dorsal pedal arteries (5 x 10-8 M). A 20-fold difference in the ED50 for nitroglycerin was observed (5 x 10-8 M in the saphenous veins and 1 x 10-6 M in the dorsal pedal arteries). Although both tissues exhibited a similar maximum inhibition of tone, a 10-fold greater concentration of nitroglycerin (2 x 10-5 M) was required in dorsal pedal arteries than in saphenous veins (2 x 10-6 M) to produce this effect. During maximal relaxation, the incubation medium was analyzed for nitroglycerin and dinitrate metabolite concentration. A concentration of dinitrate metabolite as low as 0.8% of the GTN concentration was accurately measured by the methods used. In all instances maximal relaxation occurred without the release of detectable amounts of the dinitrate metabolite into the incubation medium. These data are at variance with the generally accepted hypothesis that the metabolism of nitroglycerin occurs concomitantly with relaxation. Therefore the intact nitroglycerin molecule is essential for the initiation of relaxation in vascular smooth muscle.
ACKNOWLEDGMENTS It is a pleasure to acknowledge Mr. Sheldon Kraicer for his capable technical assistance and Mrs. Debbie Browne and Ms. Thelma Law for their excellent secretarial assistance in the preparation of the manuscript.
- Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics
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