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 Ca2+-activated potassium channel (BKCa) via guanylyl cyclase (GC)-coupled natriuretic peptide receptors (NPRs) in vascular smooth muscle cells (VSMCs). Contraction experiments were performed using human radial artery, whereas BKCa 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 BKCa, 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. BKCa 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, BKCa 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-BKCa is one possible signaling system involved in VNP induced relaxation.

• MeSH
• arteria radialis cytologie   fyziologie   účinky léků   MeSH
• arteriae mesentericae cytologie   fyziologie   účinky léků   MeSH
• atriální natriuretický faktor farmakologie   fyziologie   MeSH
• financování organizované MeSH
• guanosinmonofosfát cyklický analogy a deriváty   farmakologie   MeSH
• guanylátcyklasa fyziologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• metoda terčíkového zámku MeSH
• peptidy farmakologie   MeSH
• receptory pro atriální natriuretický faktor fyziologie   MeSH
• svaly hladké cévní cytologie   fyziologie   účinky léků   MeSH
• techniky in vitro MeSH
• tetraethylamonium farmakologie   MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí agonisté   fyziologie   MeSH
• vazodilatace fyziologie   účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH