Zygmunt P M, Grundemar L, Högestätt E D
Department of Clinical Pharmacology, Lund University, Sweden.
Acta Physiol Scand. 1994 Sep;152(1):107-14. doi: 10.1111/j.1748-1716.1994.tb09789.x.
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.
