Differential Roles of AT1 and AT2 Receptor Subtypes in Vascular Trophic and Phenotypic Changes in Response to Stimulation With Angiotensin II

The aim of this study was to investigate the roles of angiotensin II (Ang II) receptor subtypes 1 (AT1) and 2 (AT2) in producing vascular wall hypertrophy and qualitative changes in smooth muscle cell gene expression. Wistar rats were treated for 23 days with osmotic minipumps containing solvent and either Ang II (120 ng·kg−1·min−1) or PD123319 (30 mg·kg−1·d−1), an AT2 receptor antagonist. In addition, rats receiving solvent and either Ang II or PD123319 were given losartan, an AT1 receptor antagonist, in the drinking water (10 mg·kg−1·d−1). Vascular wall hypertrophy and smooth muscle phenotype were characterized by morphometric analysis combined with immunohistochemistry. Ang II–induced hypertension was associated with the development of medial hypertrophy of the aorta and coronary arteries accompanied by reversion of vascular smooth muscle cells (VSMCs) toward an immature phenotype, as shown by the expression of cellular fibronectin and nonmuscle myosin. Losartan treatment, which restored normal arteria...