Vascular expression of angiotensin type 2 receptor in the adult rat: influence of angiotensin II infusion

Objective The aim of this study was to investigate the relative role of the angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors in mediating angiotensin Ii-induced regulation of AT(2) receptor in mesenteric artery. Design Sprague-Dawley rats were infused with either angiotensin II or vehicle for 14 days at a dose of 58.3 ng/ min, Ang Ii-infused rats were allocated to receive either an AT(1) antagonist, valsartan at a dose of 30 mg/kg per day or the AT(2) receptor antagonist PD123319 at a dose of 830 ng/min. Methods Gene and protein expression of the AT(2) receptor in the mesenteric vasculature was assessed by quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry and by in vitro autoradiography with a specific radioligand, (1251)-CGp 42112B. Results The AT(2) receptor mRNA and protein were detected in the mesenteric artery from adult rats, Both nuclear emulsion and immunohistochemical staining showed expression of the AT(2) receptor in the adventitial and medial layers. Compared to control rats, angiotensin II infusion was associated with a significant increase in the AT2 receptor expression, Valsartan treatment significantly reduced AT(2) receptor gene expression, with no significant effect of PD123319 on this parameter. Conclusions This study confirms that the presence of the AT(2), receptor in mesenteric arteries in adult rats, shows an up-regulation of the AT(2) receptor following angiotensin II infusion and suggests a role for the AT(1) receptor in this regulation, In view of the recently demonstrated effects of the AT(2) receptor, these findings may be relevant to the role of the AT(2) receptor in the pathophysiology of vascular remodeling.