Vascular and adrenal receptors for atrial natriuretic factor in the rat.

Abstract

Previous studies have shown that atrial natriuretic factor, a powerful vasorelaxant of precontracted vessels, inhibits the secretion of aldosterone stimulated by angiotensin II, adrenocorticotropic hormone, and potassium. We now report the presence of specific binding sites for atrial natriuretic factor in rat blood vessels (mesenteric and renal arteries) and adrenal capsules. Radioiodinated synthetic atrial natriuretic factor bound to a single class of high-affinity (KD = 0.1 nM) low-capacity receptors in a particulate fraction from blood vessels and adrenals. Unrelated peptides did not displace atrial natriuretic factor. Fragments of atrial natriuretic factor displaced the labeled ligand with decreasing potency after cleavage at the N-terminal. The cleavage of the C-terminal tyrosine did not decrease the potency of atrial natriuretic factor, but further cleavage at the C-terminal dramatically reduced the affinity of the resulting peptides. The potency of the atrial natriuretic factor fragments in the radioligand assay was in proportion to their potency to inhibit aldosterone secretion by isolated rat glomerulosa cells. Our results suggest that these binding sites mediate the biological actions of atrial natriuretic factor in blood vessels and the adrenal, and that both receptors have similar specificities.

Specific binding of atrial natriuretic factor in brain microvessels.

“…'251-ANF, whereas nonrelated peptide hormones do not significantly displace radioactive ANF. The observed dissociation constant of 125I-ANF to brain microvessels corresponds to a high-affinity site similar to those obtained in other vascular tissues for larger vessels such as rabbit aorta (3), rat aorta (21), rat mesenteric arteries, and renal arteries (5) and in bovine aortic smooth muscle and endothelial cells (22).…”

“…4). It was observed that 125I-ANF displayed a rate of association with a half-life of about 5 was shown by dissociation with the addition of native ANF to a final concentration of 1 ,uM (Fig. 4).…”

“…Mammalian atria contain different peptides, including the atrial natriuretic factor (ANF), that possess potent diuretic, natriuretic, and vasoactive properties (1,2). ANF is released into the general circulation and has been proposed to be actively involved in blood-pressure regulation and fluid homeostasis as an antagonist of the renin-angiotensin (Ang) system through receptor-mediated actions in the kidney (3), vascular tissues (4), adrenal glands (5), and brain (6). In the brain, binding sites for ANF have been characterized in specific areas involved in blood-pressure control, such as the subfornical organ (7)-a circumventricular structure that lacks the tight capillary endothelial junctions of the blood-brain barrier and, therefore, is exposed to circulating peptides.…”

Biologically active atrial peptides

“…The inhibitory action of atrin on aldosterone release is dependent on an intact intramolecular disulfide bridge (79), similar to the structural requirement for smooth muscle relaxation (33). Specific receptors for atrin have been demonstrated in membranes prepared from adrenal glomerulosa (44,64), and receptor binding is again critically dependent on an intact disulfide bridge (44). Reduction of plasma aldosterone levels in response to atrin infusion has also been documented in anesthetized dogs (12) and in conscious rats (96 (98), although a direct effect of atrin on renin secretion by renal cortical slices has also been reported (99).…”

“…Atrial pacing (38) and paroxysmal atrial tachyarrhythmias (60) elevate circulating atrin concentrations and, in patients with congestive heart failure, plasma-atrin levels were markedly elevated above normal levels (59), indicating that chronic elevation of atrial pressures may lead to hypersecretion ofatrin. Reports ofatrin concentrations in rat plasma have been variable, with levels ranging from 20 to 550 pM (35,37,61 Ala-Arg-Thr--Gn-Gly-Leu-Leu-Gln--Phe-Ala-Leu-Leu-Leu-Leu-Phe-Ser-Val (gly) (ile)j(his) (64), and rabbit aorta (65), from rat and rabbit kidney (65) and cultured renal epithelial (LLC PK,) cells, derived from pig kidney (65).…”