Local Actions of Angiotensin II

In order to gain insight into the local actions of angiotensin II (ANG II) we have determined the distribution of a component of the effector system for the peptide, the ANG II receptor, and that of an enzyme-catalysing ANG II formation, angiotensin converting enzyme (ACE), by in vitro autoradiography in several target tissues. The superagonist ANG II analog, 125I Sar1 ANG II, or the antagonist analog, 125I Sar1,He8 ANG II, were used as specific radioligands for ANG II receptors. A derivative of the specific ACE inhibitor, lysinopril, called 125I-351 A, was used to label ACE in tissues. In the adrenal, a high density of ANG II receptors occurs in the glomerulosa zone of the cortex and in the medulla. ACE is also localized in these two zones, indicating that local production of ANG II may occur close to its sites of action in the zona glomerulosa and adrenal medulla. In the kidney, a high density of ANG II receptors is associated with glomeruli in the cortex and also with vasa recta bundles in the inner stripe of the outer medulla. ACE is found in very high concentration in deep proximal convoluted tubules of the cortex, while much lower concentrations of the enzyme occur in the vascular endothelium throughout the kidney. In the central nervous system three classes of relationships between ANG II receptors and ACE are observed: (a) In the circum-ventricular organs, including the subfornical organ and or- ganum vasculosum of the lamina terminalis, a high concentration of both components occurs. Since these structures have a deficient blood-brain barrier, local conversion of circulating angiotensin I (ANG I) to ANG II may contribute to the action of ANG II at these sites, (b) Sites within the blood-brain barrier such as the hypothalamic paraventricular nucleus, median eminence, median preoptic nucleus, and nucleus tractus solitarius – contain ANG II immu-noreactive fibres and neurons, ANG II receptor binding sites, and ACE. It seems likely that in these sites ACE may be involved in the local neuronal synthesis of ANG II. (c) In the basal ganglia, including the caudate putamen, globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata, a high density of ACE occurs without enrichment of ANG II receptors, or of ANG II-containing cells or fibres. This suggests that the enzyme may be involved in processing a neuropeptide substrate other than ANG I in the striatonigr-al pathway. These studies also indicate that, in many sites, ACE may occur close to ANG II receptors. Therefore, there is a potential for locally formed ANG II to augment the action of circulating ANG II in tissues such as the adrenal, vasculature, kidney, and central nervous system.