Vasorelaxing action of vasonatrin peptide is associated with activation of large-conductance Ca(2+)-activated potassium channels in vascular smooth muscle cells.
The aim of this study was to test the hypothesis that vasorelaxing action of vasonatrin peptide (VNP) is due to activation of the large-conductance Ca(2+)-activated potassium channel (BK(Ca)) via guanylyl cyclase (GC)-coupled natriuretic peptide receptors (NPRs) in vascular smooth muscle cells (VSMCs). Contraction experiments were performed using human radial artery, whereas BK(Ca) current by patch clamp was recorded in cells from rat mesenteric artery. Contractility of rings cut from human radial artery was detected in vitro. As a result, VNP induced 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, or methylene blue (MB), a selective inhibitor of guanylyl cyclase. Sequentially, whole-cell K(+) currents were recorded using patch clamp techniques. BK(Ca) current of VSMCs isolated from rat mesentery artery was obtained by subtracting the whole cell currents after applications of 10(-7) mol/l iberiotoxin (IBX) from before its applications. In accordance with the results of arterial tension detection, BK(Ca) current was significantly magnified by VNP, which could also be mimicked by 8-Br-cGMP, whereas suppressed by HS-142-1, or MB. Taken together, VNP acts as a potent vasodilator, and NPRA/B-cGMP-BK(Ca) is one possible signaling system involved in VNP induced relaxation.
Yu
J
J
Preclinical Experiment Center, Fourth Military Medical University, Xi'an, Shaanxi, China.
Zhu
M
M
Fu
Z
Z
Zhu
X
X
Zhao
Y
Y
Chen
B
B
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists* / Q000502:physiology; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D017534:Radial Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D000099242:Atrial Natriuretic Factor Receptor B
D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D006162:Guanylate Cyclase; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D017461:Receptors, Atrial Natriuretic Factor; D019789:Tetraethylammonium; D000099242:Atrial Natriuretic Factor Receptor B; C068986:ventricular natriuretic peptide, eel; C016276:8-bromocyclic GMP; C064719:iberiotoxin; C091715:atrial natriuretic factor receptor A