Differential sensitivity to ATP-sensitive potassium channel openers of norepinephrine-induced contraction of guinea pig and rat aorta

Abstract

Vasorelaxant effects of ATP-sensitive potassium (K ATP) channel openers were examined on the tonic phase of vascular contraction induced by norepinephrine (NE) in guinea pig and rat aorta. K ATP channel openers, NIP-121 and cromakalim, produced glibenclamide-sensitive and concentration-dependent relaxations in guinea pig and rat aorta preconstricted with NE. However, the vascular relaxations induced by both K ATP channel openers were less pronounced in guinea pig aorta than in rat aorta. d - cis-Diltiazem, at the concentration up to 10 −5 M, did not appreciably inhibit the NE-induced contraction of guinea pig aorta, whereas the compound almost completely inhibited the NE-induced contraction of rat aorta at the same concentration. By contrast, sodium nitroprusside relaxed the NE-induced contractions in both guinea pig and rat aorta with similar potencies. These findings suggest that vasorelaxant effects of K ATP channel openers on the NE-induced sustained contraction in guinea pig aorta is not attributable to the subsequent inhibition of Ca 2+ influx through L-type voltage-gated Ca 2+ channels. Lower sensitivity of guinea pig aortic smooth muscle to K ATP channel openers is most likely due to the low dependence of NE-induced contraction on the Ca 2+ influx in this vascular smooth muscle.