Differential contribution of calcium channels to α1-adrenoceptor-mediated contraction is responsible for diverse responses to cooling between rat tail and iliac arteries

Abstract

Our previous studies have shown that α1-adrenoceptors, in addition to α2-adrenoceptors, are involved in enhanced contraction of cutaneous blood vessels during cooling. The present study aimed to elucidate the mechanism underlying it. In tail and iliac arteries isolated from rats, isometric contraction was measured using a myograph and the phosphorylation level of myosin phosphatase target subunit 1 (MYPT1) was quantified by western blotting. The phenylephrine-induced contraction was enhanced by cooling to 24 °C in tail arteries, but was suppressed in iliac arteries. Endothelium denudation or treatment with iberiotoxin enhanced the phenylephrine-induced contraction in tail arteries at 37 °C; however, neither affected the contraction at 24 °C. The phenylephrine-induced contraction at 37 °C was largely suppressed by nifedipine in iliac arteries, but only slightly in tail arteries. The Rho kinase inhibitor H-1152 largely suppressed the phenylephrine-induced contraction at 24 °C, but only slightly at 37 °C, in both arteries. The phosphorylation level of MYPT1 at Thr855 in tail arteries was increased by the cooling. Taken together, these results suggest the following mechanism in regard to cooling-induced enhancement of α1-adrenoceptor-mediated contraction in tail arteries: Cooling enhances the contraction of tail arteries via α1-adrenoceptor stimulation by reducing endothelium-dependent, large-conductance Ca2+-activated K+ channel-mediated relaxation and by inducing Rho kinase-mediated Ca2+ sensitization, although the latter occurs even in iliac arteries. A smaller contribution of voltage-dependent Ca2+ channels, which are largely suppressed by cooling, to α1-adrenoceptor-mediated contraction in tail arteries seems to be more crucially involved in the appearance of the enhanced contractile response to cooling.