Angiotensin II exerts positive inotropic and chronotropic effects on the mammalian heart by binding to specific membrane receptors. Recently, two subtypes of angiotensin II receptors (AT1 and AT2) have been distinguished by using the nonpeptide antagonists losartan (previously known as DuP 753) and PD123177. To evaluate the tissue distribution and subtypes of angiotensin II receptors in rat heart, we performed a I-125-[Sar1,Ile8]angiotensin II in situ binding assay on tissue sections obtained from adult Sprague-Dawley rats (10 and 14 weeks old). 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 the receptors was quantified 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 the atria, right and left ventricles, intraventricular septum, and sinoatrial node, whereas it was significantly greater in the atrioventricular node. The AT1 receptor appears to interact with guanidine nucleotide regulatory proteins, because GTP-gamma-S causes dissociation of the radioligand from this receptor. In contrast, the AT2 receptor does not appear to directly interact with guanine nucleotide regulatory proteins, inasmuch as radioligand dissociation from this receptor subtype is not affected by GTP-gamma-S. Because angiotensin II has been reported to have growth-potentiating effects in several tissues, we examined angiotensin II receptors in fetal (embryonic days 16 and 19) and neonatal (1-, 2-, 3-, and 10-day-old) rats. A twofold increase in the density of both receptor subtypes was found immediately after birth, reaching a maximum on day 2 and decreasing toward prenatal values thereafter. Thus, in rat heart, AT1 and AT2 receptors are equally distributed over the myocardium. The density of these angiotensin II receptors is developmentally regulated.
CHARACTERIZATION OF ANGIOTENSIN-II RECEPTOR SUBTYPES IN RAT-HEART
SECHI, Leonardo Alberto;
1992-01-01
Abstract
Angiotensin II exerts positive inotropic and chronotropic effects on the mammalian heart by binding to specific membrane receptors. Recently, two subtypes of angiotensin II receptors (AT1 and AT2) have been distinguished by using the nonpeptide antagonists losartan (previously known as DuP 753) and PD123177. To evaluate the tissue distribution and subtypes of angiotensin II receptors in rat heart, we performed a I-125-[Sar1,Ile8]angiotensin II in situ binding assay on tissue sections obtained from adult Sprague-Dawley rats (10 and 14 weeks old). 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 the receptors was quantified 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 the atria, right and left ventricles, intraventricular septum, and sinoatrial node, whereas it was significantly greater in the atrioventricular node. The AT1 receptor appears to interact with guanidine nucleotide regulatory proteins, because GTP-gamma-S causes dissociation of the radioligand from this receptor. In contrast, the AT2 receptor does not appear to directly interact with guanine nucleotide regulatory proteins, inasmuch as radioligand dissociation from this receptor subtype is not affected by GTP-gamma-S. Because angiotensin II has been reported to have growth-potentiating effects in several tissues, we examined angiotensin II receptors in fetal (embryonic days 16 and 19) and neonatal (1-, 2-, 3-, and 10-day-old) rats. A twofold increase in the density of both receptor subtypes was found immediately after birth, reaching a maximum on day 2 and decreasing toward prenatal values thereafter. Thus, in rat heart, AT1 and AT2 receptors are equally distributed over the myocardium. The density of these angiotensin II receptors is developmentally regulated.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
