Modulation of kinin B1 receptor expression by endogenous angiotensin II in hypertensive rats

We investigated the expression and localization of B I receptor in tissues of rats submitted to a renin-dependent model of hypertension (2K-IC), and analyzed the influence of endogenous Ang II in modulating the in vivo expression of these receptors. B1 mRNA levels in the heart, kidney and thoracic aorta were quantified by real time PCR, B1 receptor protein expression was assessed by immunchistochemistry, plasma Ang II levels were analyzed by radioirnmunoassay and the effects of ATI receptor blockade were determined after losartan treatment. 2K-IC rats presented a marked increase in Ang II levels when compared to sham-operated rats. In parallel, cardiac- (but not renal and aortic) B I mRNA levels were 15-fold higher in 2K-IC than in sham rats. In 2K-IC, B1 expression was detected in the endothelium of small cardiac arteries and in cardiomyocytes. Losartan completely reverted the increased B1 mRNA levels and significantly decreased the protein expression observed in 2K-IC rats, despite reducing, but not normalizing blood pressure. We conclude that in the 2K-IC rat, induction of cardiac B I receptor might be tightly linked to ATI receptor activation. These data suggest the existence of a new site of interaction between kinins and angiotensins, and might provide important contributions for a better understanding of the pathophysiology of hypertension. (c) 2006 Elsevier B.V. All rights reserved.