Urotensin II promotes aldosterone expression in rat aortic adventitial fibroblasts.

Abstract

Urotensin II (UII) contributes to cardiovascular diseases by activating vasoactive peptides. The present study aimed to determine the effect of UII on aldosterone (ALD) and its receptor in cultured adventitial fibroblasts (AFs) and the tunica adventitia of rat vessels to explore the possible mechanisms underlying vascular remodeling. Expression levels of aldosterone and its receptor on tunica adventitia were determined using immunohistochemistry. Growth-arrested AFs and tunica adventitia from rat vessels were incubated with UII and inhibitors of various signal transduction pathways. ALD receptor (ALD-R) mRNA expression levels and ALD protein exoression levels were determined by reverse transcription-quantitative polymerase chain reaction and ELISA, respectively. Aldosterone and its receptors were expressed on tunica adventitia. UII promoted ALD protein secretion from cells in a dose- and time-dependent manner. ALD-R mRNA expression in cells was also dysregulated. Furthermore, the effects of UII were substantially inhibited by treatment with the inhibitors PD98059, Y-27632, H-7, CSA and nicardipine. These results were further verified in the tunica adventitia of rat vessels. The present findings indicated that UII stimulated ALD protein secretion and ALD-R mRNA expression in AFs and in the tunica adventitia of rat vessels; moreover, this effect may be mediated by signal transduction pathways involving MAPK, Rho, PKC, calcineurin and Ca2+. UII may also contribute to vascular remodeling by stimulating the production of ALD and its receptor.