Physiological Role of Silent Receptors of Atrial Natriuretic Factor

TLDR

A ring‑deleted ANF analog binds with high affinity to ~99 % of renal ANF receptors in isolated perfused rat kidneys. In intact anesthetized rats, C‑ANF 4‑23 increases sodium excretion and lowers blood pressure by raising plasma endogenous ANF, demonstrating that most renal ANF receptors are biologically silent and likely serve as peripheral storage‑clearance sites that buffer plasma ANF levels.

Abstract

A ring-deleted analog of atrial natriuretic factor—des[Gln 18 , Ser 19 , Gly 20 , Leu 21 , Gly 22 ] ANF 4-23 -NH 2 (C-ANF 4-23 )—binds with high affinity to approximately 99% of ANF receptors in the isolated perfused rat kidney. In this preparation, C-ANF 4-23 is devoid of detectable renal effects and does not antagonize any of the known renal hemodynamic and natriuretic actions of biologically active ANF 1-28 . In contrast, both C-ANF 4-23 and ANF 1-28 increase sodium excretion and decrease blood pressure in intact anesthetized rats. This apparent contradiction is resolved by the finding that the ring-deleted analog markedly increases plasma levels of endogenous immunoreactive ANF in the rat. The results show that the majority of the renal receptors of ANF are biologically silent. This new class of receptors may serve as specific peripheral storage-clearance binding sites, acting as a hormonal buffer system to modulate plasma levels of ANF.