Open AccessVasorelaxing Action of Vasonatrin Peptide is Associated with Activation of Large-Conductance Ca2+-activated Potassium Channels in Vascular Smooth Muscle Cells
Author(s) -
Jun Yu,
Miao-Zhang Zhu,
Zhaojun Fu,
Xiang Yang Zhu,
Yu Zhao,
B Chen
Publication year - 2010
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931746
Subject(s) - iberiotoxin , vascular smooth muscle , vasodilation , potassium channel , patch clamp , charybdotoxin , chemistry , mesenteric arteries , artery , medicine , natriuretic peptide , contractility , biophysics , electrical impedance myography , endocrinology , receptor , biochemistry , biology , smooth muscle , heart failure
The aim of this study was to test the hypothesis thatvasorelaxing action of vasonatrin peptide (VNP) is due toactivation of the large-conductance Ca2+-activated potassiumchannel (BKCa) via guanylyl cyclase (GC)-coupled natriureticpeptide receptors (NPRs) in vascular smooth muscle cells(VSMCs). Contraction experiments were performed using humanradial artery, whereas BKCa 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 BKCa, 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. BKCa 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, BKCa 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-BKCa is one possiblesignaling system involved in VNP induced relaxation.