Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

Abstract

Right ventricular myocardial hypertrophy during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in this setting has never been investigated. We have therefore examined the chronic hypoxia pattern of AT1 and AT2expression in the right and left cardiac ventricles, using in situ binding and RT-PCR assays. Hypoxia produced right, but not left, ventricular hypertrophy after 7, 14, and 21 days, respectively. Hypoxia for 2 days was associated in each ventricle with a simultaneous and transient increase ( P < 0.05) in AT1 binding and AT1 mRNA levels in the absence of any significant change in AT2 expression level. Only after 14 days of hypoxia, AT2 binding increased ( P < 0.05) in the two ventricles, concomitantly with a right ventricular decrease ( P < 0.05) in AT2 mRNA. Along these data, AT1 and AT2 binding remained unchanged in both the left and hypertrophied right ventricles from rats treated with monocrotaline for 30 days. These results indicate that chronic hypoxia induces modulations of AT1 and AT2 receptors in both cardiac ventricles probably through direct and indirect mechanisms, respectively, which modulations may participate in myogenic (at the level of smooth or striated myocytes) rather than in the growth response of the heart to hypoxia.