The basal endothelial inhibitory influence on vascular tone is not affected in nitroglycerin-tolerant rat aorta.
Prolonged exposure to nitrovasodilators produces tolerance and dependence. Nitrovasodilators exert their action on vascular smooth muscle cells by activation of guanylyl cyclase. Nitrates share this mechanism with endothelial NO, which exerts a continuous inhibitory influence on vascular tone. Whether the basal inhibitory endothelial influence might be affected in rat aorta exposed in vitro to a tolerance-inducing concentration of nitroglycerin was investigated in this study. It was found that the basal inhibitory influence, assessed as its inhibitory influence on norepinephrine-induced contraction, and as the contractile effect of N-nitro-L-arginine methyl ester or methylene blue, was the same in nitroglycerin-tolerant and control aortic rings. Our results give an indication that changes in basal inhibitory endothelial influence are not involved in the phenomena of nitrate tolerance and nitrate dependence.
Department of Physiology and Physiopathology, University of Gent, Belgium.
J
J
Van de Voorde
S
S
Vyt
B
B
Vanheel
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004361:Drug Tolerance; D004727:Endothelium / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D011460:Prostaglandins F; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine