Vasorelaxing Action of Vasonatrin Peptide is Associated withActivation of Large-Conductance Ca~(2+)-activated Potassium Channelsin Vascular Smooth Muscle Cells

摘要

The aim of this study was to test the hypothesis thatvasorelaxing action of vasonatrin peptide (VNP) is due toactivation of the large-conductance Ca~(2+)-activated potassiumchannel (BK_(Ca))viaguanylyl cyclase (GC)-coupled natriureticpeptide receptors (NPRs) in vascular smooth muscle cells(VSMCs). Contraction experiments were performed using humanradial artery, whereas BK_(Ca)current by patch clamp was recordedin cells from rat mesenteric artery. Contractility of rings cut fromhuman radial artery was detected in vitro. As a result, VNPinduced a dose-dependent vasorelaxation of human radial artery,which could be mimicked by 8-Br-cGMP, and suppressed by TEA,a blocker of BK_(Ca), HS-142-1, a blocker of GC-coupled NPRs, ormethylene blue (MB), a selective inhibitor of guanylyl cyclase.Sequentially, whole-cell K~+currents were recorded using patchclamp techniques. BK_(Ca)current of VSMCs isolated from ratmesentery artery was obtained by subtracting the whole cellcurrents after applications of 10~(-7)mol/l iberiotoxin (IBX) frombefore its applications. In accordance with the results of arterialtension detection, BK_(Ca) current was significantly magnified byVNP, which could also be mimicked by 8-Br-cGMP, whereassuppressed by HS-142-1, or MB. Taken together, VNP acts as apotent vasodilator, and NPRA/B-cGMP-BK_(Ca)is one possiblesignaling system involved in VNP induced relaxation.