Renal atrial natriuretic peptide receptor subtypes in spontaneously hypertensive rats

Abstract

Receptor subtypes for atrial natriuretic peptide (ANP) were characterized in kidneys of 18-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) by in vitro autoradiography through use of des[Gln18, Ser19, Gly20, Leu21, Gly22] ANP-(4–23) (C-ANP) and ANP-(5–25) as subtype-selective ligands. alpha-125I-ANP (100 pM) bound reversibly but with high affinity to glomeruli, to stripes in outer medulla, and to inner medulla of both WKY and SHR. C-ANP (10 microM) inhibited approximately 70% of the glomerular binding but none of the medullary binding in either strain. All high-affinity specifically reversible binding sites for alpha-ANP that bound C-ANP were also bound by 10 microM ANP-(5–25). However, the specifically reversible binding of alpha-125I-ANP that was not inhibited by 10 microM C-ANP behaved differently in each strain. In WKY, this binding was weakly inhibited by ANP-(5–25), so that even the presence of 10 microM ANP-(5–25) did not inhibit some glomerular binding and greater than 40% of the specifically reversible medullary binding of alpha-125I-ANP. In SHR, this binding was inhibited by ANP-(5–25) with a significantly higher affinity so that all specifically reversible binding of alpha-125I-ANP was inhibited by 10 microM ANP-(5–25). SHR also showed higher affinities but lower maximum binding capacities for alpha-ANP in their outer cortical glomeruli and medullas. These results suggest that the preponderant medullary ANP receptor differs between WKY and SHR. Differences in glomerular subtypes of ANP receptor may also distinguish WKY and SHR.