QUANTIFICATION AND LOCALIZATION OF ANGIOTENSIN-II RECEPTORS AND ANGIOTENSIN-CONVERTING ENZYME IN THE DEVELOPING RAT-HEART

Objective: The aim was to determine the quantification and localisatio n of angiotensin II receptors and angiotensin converting enzyme (ACE) in the developing rat heart. Methods: Quantitative autoradiography was used to determine the density of [I-125]Sar(1)-angiotensin II binding to angiotensin II receptors and the density of [I-125]351A binding to ACE. Results: Angiotensin ii receptors were first detected in the myo cardium on embryonic day 14, and reached a maximum density within the first postnatal week. During the perinatal period, the density of angi otensin II receptors was twofold higher in atrial than in ventricular myocardium [27(SEM 7) v 11(1) fmol . mg(-1) protein]. By adulthood, ho wever, the density of angiotensin II receptors did not differ between atria and ventricles. A high density of angiotensin II receptors was f irst detected in the cardiac vasculature on embryonic day 19, with bin ding density decreasing during development. During the embryonic and e arly postnatal periods, most of the binding in the cardiac vasculature was to AT(2) receptors. ACE was first detected in the myocardium on t he day of birth, with the density of binding to ACE increasing during development. On postnatal day 56, the density of binding to ACE was fo urfold higher in atrial than in ventricular myocardium [99(22) v 22(4) fmol . mg(-1) protein]. A moderate density of binding to ACE was firs t detected in the cardiac vasculature and heart valves on embryonic da y 19, with binding density increasing during development. By adulthood , the density of binding to ACE was 10- to 25-fold higher in the cardi ac vasculature and heart valves than in the myocardium. Conclusions: T he density of angiotensin II receptors and the density of binding to A CE are developmentally regulated in the heart. Both AT(1) and AT(2) re ceptors were present in the rat heart by late gestation and could, the refore, mediate the effects of angiotensin II on early cardiac growth and development.