Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PRESENCE OF ANGIOTENSIN II AT2 RECEPTOR BINDING SITES IN THE ADVENTITIA OF HUMAN KIDNEY VASCULATURE

Abstract

1. Angiotensin II (AngII) receptor subtypes in adult human kidney were pharmacologically characterized by in vitro autoradiography using the AngII receptor subtype-selective antagonists, losartan and PD 123319, and the sensitivity to the reducing agent, dithiothreitol. 2. High densities of AngII AT(1) receptor binding occur in the glomeruli and the inner stripe of the outer medulla, while a moderate AT(1) receptor binding is localized in the proximal convoluted tubules. 3. AT(2) receptor binding is observed predominantly in the intrarenal large blood vessels, including the arcuate, inter- and intra-lobular arteries, and in the renal capsule. 4. In the major renal artery, AT(1) receptor binding is abundant in the media and adventitia, while AT(2) receptor binding is observed mainly in the adventitia. 5. At the light microscopic level using emulsion autoradiography, AT(1) receptors are localized in the glomeruli and juxtaglomerular apparatus, as expected. However, in larger renal blood vessels, including the arcuate arteries, inter- and intra-lobular arteries, intense AT(2) receptor labelling occurs primarily in the adventitia, while the endothelium and vascular smooth muscle layers contain only low levels of AngII receptor binding. 6. These results indicate that the adult human kidney displays two pharmacologically distinct AngII receptor subtypes, with AT(1) predominating in the glomeruli, juxtaglomerular apparatus, proximal tubules and the inner stripe of the outer medulla, while AT(2) predominates in the adventitia of the arcuate and interlobular arteries and the renal capsule. The functional significance of AT(2) receptor binding sites in the adventitia of adult human kidney vessels remains to be elucidated.