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

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.

Effects of Extremely Low Doses of Arginine Vasopressin on the Renal Function in Two-kidney One Clip Goldblatt Hypertensive Rabbit / 대한신장학회잡지

It has been suggested that arginine vasopressin is involved in the acute, but not chronic, regulation of blood pressure. It is still debatable on the role of arginine vasopressin in the development and maintenance of high blood pressure, especially in renal hypertension. This study was performed to examine antidiuretic and renal hemodynamic effects of extremely low doses of arginine vasopressin and the modification of the effects in the early phase of two-kidney one clip Goldblatt hypertensive rabbits. Very low doses(up to 10-20mole/kg/min) of intrarenal arginine vasopressin induced decreases in urine volume, free water clearance, glomerular filteration rate and renal plasma flow(CPAH). The renal effects of arginine vasopressin were dose-dependent. These data indicate that the sensitivity of the kidney to decrease urine volume in response to arginine vasopressin is at least three orders of magnitude higher than previously reported. The renal effects of arginine vasopressin was significantly attenuated by the pretreatment of V2-receptor antagonist. The antidiuretic and renal hemodynamic effects elicited by very low doses of intrarenal arginine vasopressin were suppressed in the contralateral unclipped kidney of two-kidney, one clip Goldblatt hypertensive rabbits. These data suggest that the renal functions can be regulated normally by an extremely low concentration of plasma arginine vasopressin and the regulatory mechanism controlled by the ultralow plasma levels of arginine vasopressin is suppressed in the early phase of two-kidney, one clip Goldblatt hypertension.

Effects of Intrarenal Arterial Infusion of Arginine Vasopressin on the Renal Function and Renin Release in Conscious Rabbits / 대한신장학회잡지

Arginine vasopressin(AVP) released from the posterior pituitary gland is well known to cause an increase in blood pressure, antidiuresis, natriuresis and inhibition of renin secretion. However, the mechanism involved in AVP-induced natriuresis is still unknown. To investigate the mechanism of AVP- induced natriuresis, different doses of AVP were infused into the left renal artery for 10 min and renal function and data were obtained in unanesthetized rabbits. Infusion of different doses of AVP (0.3pg/kg/min-10,000pg/kg/min) caused marked decreases in urine volume, renal blood flow, glomerular filtration rate and free water clearance without changes in blood pressure. Changes in renal function by AVP were not dose-dependent but it took more time for the renal function to recover with increasing doses. Infusion of large doses of AVP(3,000, 10,000pg/kg/min) caused increases in sodium excretion in both kidneys without changes in blood pressure. Infusion of AVP caused a decrease in renin secretion rate. In indomethacin-treated rabbits, changes in urine volume and renal hemodynamics by AVP were markedly accentuated whereas natriuretic effects were attenuated. However, a marked natriuresis caused by AVP in control right kidney still persistently existed. These results suggest that the AVP-induced natriuresis may occur in two-different ways: one is indirect hormonal including prostaglandins and the other is tubular.