[Angiotensin receptors in the rat myocardium during pre- and postnatal development]

Angiotensin II exerts positive inotropic and chronotropic effects on mammalian heart by binding to specific membrane receptors. Recently, 2 subtypes of angiotensin II receptors (AT1 and AT2) have been distinguished using the nonpeptide antagonists losartan and PD123177. Because angiotensin II has been reported to have growth potentiating effects in several tissues, we examined angiotensin II receptors in fetal (embryonic day 16 and 19), neonatal (1, 2, 3 and 10 days), and adult (10 and 16 weeks) rats. We performed an 125I-[Sar1,Ile8]-angiotensin II in situ binding assay on tissue sections obtained from Sprague-Dawley rats. Binding specificity was verified by competition with unlabeled [Sar1]-angiotensin II. Distribution of AT1 and AT2 receptors was determined by competition with losartan and PD123177, respectively, and the density of receptors quantitated by emulsion autoradiography. Angiotensin II receptors were widely distributed throughout the heart, with each receptor subtype accounting for approximately 50% of the specific binding. Binding density was comparable in right and left ventricles, and interventricular septum. Throughout cardiac development a significant increase (p < 0.005) in the density of both receptor subtypes was found immediately after birth, reaching a maximum on day 2, and decreasing toward prenatal values thereafter. No variation in the proportion of the 2 receptor subtypes was observed during development. Thus, in rat heart, AT1 and AT2 receptors are equally distributed over the myocardium. The density of these angiotensin II receptors is developmentally regulated, suggesting a possible role of the cardiac renin-angiotensin system in heart growth and in the adaptation of the heart to postnatal circulatory conditions.