Urotensin II receptor antagonist attenuates monocrotaline-induced cardiac hypertrophy in rats.
Urotensin II (UII) is a vasoactive peptide with potent cardiovascular effects through a G protein-coupled receptor. Hypoxia stimulates the secretion of UII and atrial natriuretic peptide (ANP). However, the effect of UII on hypoxia-induced cardiac hypertrophy is still controversial. The present study was conducted to determine whether human UII (hUII)-mediated ANP secretion influences hypoxia-induced cardiac hypertrophy using in vitro and in vivo models. Hypoxia caused an increase in ANP secretion and a decrease in atrial contractility in isolated perfused beating rat atria. hUII (0.01 and 0.1 nM) attenuated hypoxia-induced ANP secretion without changing the atrial contractility, and the hUII effect was mediated by the UII receptor signaling involving phospholipase C, inositol 1,3,4 trisphosphate receptor, and protein kinase C. Rats treated with monocrotaline (MCT, 60 mg/kg) showed right ventricular hypertrophy with increases in pulmonary arterial pressure and its diameter and plasma levels of UII and ANP that were attenuated by the pretreatment with an UII receptor antagonist, urantide. An acute administration of hUII (5 μM injection plus 2.5 μM infusion for 15 min) decreased the plasma ANP level in MCT-treated rats but increased the plasma ANP level in MCT plus urantide-treated and sham-operated rats. These results suggest that hUII may deteriorate MCT-induced cardiac hypertrophy mainly through a vasoconstriction of the pulmonary artery and partly through the suppression of ANP secretion.
Gao
Shan
S
Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Korea.
Oh
Young-Bin
YB
Shah
Amin
A
Park
Woo Hyun
WH
Chung
Myoung Ja
MJ
Lee
Young-Ho
YH
Kim
Suhn Hee
SH
D000818:Animals; D016275:Atrial Function / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D006801:Humans; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007262:Infusions, Intravenous; D055104:Infusions, Subcutaneous; D008297:Male; D016686:Monocrotaline; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014579:Urotensins / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
D002316:Cardiotonic Agents; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; D016686:Monocrotaline; D009320:Atrial Natriuretic Factor; C029677:urotensin II