Endothelium-independent and -dependent vasoactivity of 6-nitronorepinephrine

Abstract

Vasoactivities of 6-nitronorepinephrine were investigated using rat aorta. 6-Nitronorepinephrine (>100 μM) caused dose-dependent contraction in both endothelium-intact and -denuded aorta, although the latter showed greater contraction than the former. Prazosin (>3 nM), an α 1-adrenoceptor antagonist, attenuated significantly the 6-nitronorepinephrine-induced contractions, thereby suggesting the α 1-adrenoceptor involvement. Aortic rings prepared from reserpine-pretreated rats showed the 6-nitronorepinephrine-induced a contraction to the extent similar to those from untreated rats, suggesting that endogenous norepinephrine does not play a role in the 6-nitronorepinephrine-induced contraction. 6-Nitronorepinephrine (>10 μM) potentiated norepinephrine-induced contraction only in the presence of endothelium. The augmentation was attenuated by catalase (1200 U/ml). H 2O 2 (10–300 μM) augmented the norepinephrine-induced contraction only in the endothelium-intact rat aortic rings. 6-Nitronorepinephrine attenuated significantly acetylcholine-induced relaxation. Catalase prevented the 6-nitronorepinephrine-induced inhibition of the acetylcholine-induced relaxation. These results suggest that 6-nitronorepinephrine has a weak α 1-adrenoceptor agonistic property and that the endothelium-dependent potentiation by 6-nitronorepinephrine of the norepinephrine-induced contraction is mediated through production of H 2O 2.