F Bonnet1, M E Cooper, R M Carey, D Casley, Z Cao. 1. Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg West, Victoria, Australia.
Abstract
OBJECTIVE: The aim of this study was to investigate the relative role of the angiotensin type 1 (AT1) and type 2 (AT2) receptors in mediating angiotensin II-induced regulation of AT2 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 AT1 antagonist, valsartan at a dose of 30 mg/kg per day or the AT2 receptor antagonist PD123319 at a dose of 830 ng/min. METHODS: Gene and protein expression of the AT2 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 AT2 receptor mRNA and protein were detected in the mesenteric artery from adult rats. Both nuclear emulsion and immunohistochemical staining showed expression of the AT2 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 AT2 receptor gene expression, with no significant effect of PD123319 on this parameter. CONCLUSIONS: This study confirms that the presence of the AT2 receptor in mesenteric arteries in adult rats, shows an up-regulation of the AT2 receptor following angiotensin II infusion and suggests a role for the AT1 receptor in this regulation. In view of the recently demonstrated effects of the AT2 receptor, these findings may be relevant to the role of the AT2 receptor in the pathophysiology of vascular remodeling.
OBJECTIVE: The aim of this study was to investigate the relative role of the angiotensin type 1 (AT1) and type 2 (AT2) receptors in mediating angiotensin II-induced regulation of AT2 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 AT1 antagonist, valsartan at a dose of 30 mg/kg per day or the AT2 receptor antagonist PD123319 at a dose of 830 ng/min. METHODS: Gene and protein expression of the AT2 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 AT2 receptor mRNA and protein were detected in the mesenteric artery from adult rats. Both nuclear emulsion and immunohistochemical staining showed expression of the AT2 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 AT2 receptor gene expression, with no significant effect of PD123319 on this parameter. CONCLUSIONS: This study confirms that the presence of the AT2 receptor in mesenteric arteries in adult rats, shows an up-regulation of the AT2 receptor following angiotensin II infusion and suggests a role for the AT1 receptor in this regulation. In view of the recently demonstrated effects of the AT2 receptor, these findings may be relevant to the role of the AT2 receptor in the pathophysiology of vascular remodeling.
Authors: Dong You; Laurent Loufrani; Celine Baron; Bernard I Levy; Robert E Widdop; Daniel Henrion Journal: Circulation Date: 2005-02-14 Impact factor: 29.690