Expressions of Urotensin II and Urotensin II Receptor are Up-regulated in Cardiovascular Tissues in Experimentally Induced Endotoxaemia

Abstract

Urotensin II (UII) is a cyclic, vasoactive neuropeptide identified as the ligand for a novel G-protein coupled receptor, referred to as the UT-II receptor (UT-IIR). Recent studies have indicated that cardiovascular effects of UII are mediated by its receptor, UT-IIR. UII promotes hypertrophy of cardiac myocytes, and its expression is up-regulated in infarcted rat heart and in congestive heart failure in humans. Expression of UT-IIR is low to undetectable in the healthy myocardium, but is up-regulated in the ischemic and post-infarct myocardium. The expression of UT is increased by interferon-gamma, suggesting a possible up-regulation of UII and UT-IIR as a consequence of an inflammatory response, which may lead to adverse cardiac remodeling. Accordingly, we examined the expression and localization of UII and its receptor in the cardiovascular tissues of rat after treatment with lipopolysaccharide (LPS) endotoxin. Male Sprague-Dawley rats were sacrificed at 1 hr after intra-peritoneal injection of LPS at 10 mg/kg weight, or saline as control. Cardiovascular tissues were dissected out and homogenized, and the expression of UII and UT-IIR mRNA was determined by RT-PCR. We found that UT-IIR expression was markedly increased by LPS in the left and right atria, thoracic artery and mesenteric artery (MA), but not in the left and right ventricles where high basal levels of UT-IIR expression were observed even without LPS stimulation. On the other hand, UII expression was significantly increased by LPS in almost all of the cardiovascular tissues tested, except in MA where there was no significant UII expression in both the control and LPS-treated animals. In conclusion, our results show that the expression of UII and UT-IIR receptor in cardiac tissues is up-regulated in inflammatory conditions and this might contribute to myocardial dysfunction in septic shock.