ANGIOTENSIN RECEPTOR-SITES IN RENAL VASCULATURE OF RATS DEVELOPING GENETIC-HYPERTENSION

The purpose of the present study was to characterize angiotensin II (ANG II) receptors in renal resistance vessels of young spontaneously hypertensive rats (SHR). ANG II receptor subtypes were evaluated in biochemical and functional terms using nonpeptide ANG II antagonists of the types AT1 (Dup-753 and Dup-532) and AT2 (PD-123319 and CGP-42112). In vitro radiolabeled ligand binding studies were performed on preglomerular resistance vessels freshly isolated from kidneys of SHR and Wistar-Kyoto (WKY) rats. The method of isolation and purification of renal microvessels was based on iron oxide infusion into the kidneys and separation of the vessels with the aid of a magnetic field followed by successive passages through various sized sieves. Physiological receptor expression was evaluated in vivo by measuring renal blood flow responses to ANG II injected alone and in a mixture with a receptor antagonist into the renal artery of indomethacin-treated rats. Our results indicate the existence of at least two functional (vasoconstriction mediating) subtypes of ANG II receptor sites in the renal microcirculation. Eighty percent of the ANG II receptor sites displayed high affinity to Dup-753 and Dup-532 and low affinity to PD-123319 and CGP-42112, whereas the remaining 20% of sites showed low affinity to Dup-753 and Dup-532 and CGP-42112 and intermediate affinity to PD-123319. In addition, the renal vasculature of young SHR and WKY displays similar ANG II receptor characteristics and identical blood flow responses to ANG II and to mixtures of ANG II and its antagonists.