Endothelium-dependent relaxation resistant to N omega-nitro-L-arginine in the rat hepatic artery and aorta.
Nitric oxide (NO)-independent pathways contributing to acetylcholine (ACh)-induced relaxation were examined in the rat isolated hepatic artery and aorta at low and high levels of precontraction induced by phenylephrine (PhE). In the hepatic artery, the ACh-induced relaxation was unaffected by the NO synthase inhibitors N omega-nitro-L-arginine (L-NOARG, 0.3 mM) and N omega-nitro-L-arginine methyl ester (0.1 mM) at either level of pre-contraction. In the aorta, L-NOARG virtually abolished the ACh-induced relaxation at a high level, but only partially reduced the response at a low level of precontraction. Methylene blue (10 microM) and indomethacin (10 microM) did not affect the ACh-induced relaxation in the hepatic artery. L-NOARG completely inhibited the cGMP and cAMP increases induced by ACh in both types of artery. In the presence of L-NOARG, ACh was unable to relax the hepatic artery precontracted by K+. The sensitivity to PhE was increased less by L-NOARG (threefold) than after endothelial denudation (tenfold) in the hepatic artery, whereas no such difference was observed in the aorta. The relaxation induced by the NO donor 3-morpholino-sydnonimin did not differ between the arteries after endothelial denudation. These results are compatible with the existence of an endothelium-dependent inhibitory pathway distinct from the NO and cyclooxygenase pathways. This pathway seems to contribute more to the ACh-induced relaxation in the hepatic artery than in the aorta, whereas the opposite appears to be true for the NO pathway.
Zygmunt
P M
PM
Department of Clinical Pharmacology, Lund University, Sweden.
Grundemar
L
L
Högestätt
E D
ED
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019335:Nitroarginine; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D010656:Phenylephrine; D019335:Nitroarginine; D001120:Arginine; D000242:Cyclic AMP; D006152:Cyclic GMP; D000109:Acetylcholine; D011188:Potassium