Effects of Intrarenal Arterial Infusion of Atrial Natriuretic Peptide Analogs on Renal Function in Unanesthetized Rabbits / 대한신장학회잡지

ABSTRACT

BACKGROUND: Atrial cardiomyocytes synthesize, store and release atrial natriuretic peptide(ANP) which has potent physiological effects, including natriuresis, diuresis, relaxation of vascular smooth muscle and inhibition of aldosterone and renin secretion. A family of atrial peptides are derived from a precursor proANP. However, the structure-activity relationship of several C-terminal ANPs are not yet well documented. METHODS: The effects of structural difference of ANP analogs on the renal function were studied with a sensitive and reproducible bioassay using intrarenal arterial infusion in unanesthetized rabbits. RESULTS: Rat ANP-(1-28)(rANP, 12-Ile), a-human ANP-(1-28)(hANP, 12-Met), atriopeptin III [APIII, rANP-(5-28)], atriopeptin II[APII, rANP-(5- 27)], atriopeptin I[API, rANP-(5-25)], a-human ANP- (7-28)[hANP-(7-28)], and ANP fragments(13-28) [ANP-(13-28)] and (17-28)[ANP-(17-28)] were infused into left renal artery. No significant differences were observed between rANP and hANP. Diuretic and natriuretic activities of APIII were significantly lower than those of rANP and hANP, but were similar to those of hANP-(7-28). Diuretic and natriuretic effects of APII were similar to rANP and hANP in terms of peak responses. Duration of the effects of APII were longer than those of rANP and hANP. No significant changes were observed by infusions of API, and ANP fragments, ANP-(13-28) and ANP-(17-28). rANP, hANP and APIII decreased active but increased inactive renin secretion. CONCLUSION: These data suggest that substitution of isoleucine to methionine at 12 position of ANP does not affect the renal effects of ANP and that disulfide bond and C-terminal segment of ANP are important for the possession of natriuretic and diuretic activities.