Effects of ANP-(95-126) in dogs before and after induction of heart failure

Abstract

In conscious dogs with and without congestive heart failure, we investigated hemodynamic, hormonal, and renal effects of a new natriuretic peptide [ANP-(95-126)]. Unlike ANP-(99-126), which is secreted in the heart and rapidly inactivated in the kidney, ANP-(95-126) most likely originates from the kidney and is not destroyed by proteolysis in membrane preparations of kidney cortex. In healthy animals intravenous ANP-(95-126) significantly decreased mean arterial pressure, cardiac output, stroke volume, and right atrial pressure and increased heart rate without changing mean pulmonary arterial pressure and total peripheral vascular resistance. In dogs with congestive heart failure, ANP-(95-126) showed no effects on mean arterial pressure, cardiac output, stroke volume, and peripheral vascular resistance but reduced right atrial pressure and pulmonary arterial pressure. Both, in dogs before and after the induction of heart failure, the new peptide led to a significant increase of urine flow and sodium and chloride excretion. In healthy dogs there were indirect indications for a small inhibitory effect on renin and aldosterone secretion. Thus, in contrast to the considerable attenuation of renal effects of ANP-(99-126) in heart failure, the efficacy of ANP-(95-126) on renal excretory function is well preserved, which may be because of the lack of proteolytic degradation in the kidney. These results suggest that ANP-(95-126) may have clinical implications for the treatment of patients with congestive heart failure.

Hydrolysis of iodine labelled urodilatin and ANP by recombinant neutral endopeptidase EC. 3.4.24.11

“…In normal subjects, bolus injections of URO induced natriuresis and diuresis, which were twice as large as those obtained with similar doses of ANP (Saxenhofer et al, 1990). Similar findings were documented in rats (Abassi et al, 1992b) and dogs (Riegger et al, 1990;Villarreal et al, 1991) with experimental congestive heart failure (CHF).…”

“…by others, and was shown to have a very flexible N-terminal segment (Kobayashi et al, 1988 (Cody et al, 1986) or experimental animals (Riegger et al, 1988;Hoffman et al, 1988;Abassi et al, 1990; with congestive heart failure (CHF) is attenuated, and even blunted in severe stages of the disease. In contrast, infusion of equimolar doses of URO into rats with CHF (Abassi et al, 1992b) or dogs with CHF (Riegger et al, 1990;Villarreal et al, 1991), and into healthy individuals and animals (Saxenhofer et al, 1990;Hildebrandt et al, 1992;Bestle & Bie, 1993), increased sodium excretion more than ANP. These differences in the potency of URO and ANP at the renal level may be explained partially by the relative resistance of URO to NEP, so that it reaches its target, namely, the distal segment of the nephron, in greater amounts, and thereby induces greater sodium excretion.…”

“…Infusion of either ANP or URO into experimental animals (Villarreal et al, 1991;Abassi et al, 1992b;Hildebrandt et al, 1992) and man (Saxenhofer et al, 1990;Kentsch et al, 1992) induces significant natriuresis, diuresis and a reduction of blood pressure. In some studies, URO was found to be more potent than ANP (Riegger et al, 1990;Saxenhofer et al, 1990;Abassi et al, 1992b;Hildebrandt et al, 1992;Bestle & Bie, 1993). In normal subjects, bolus injections of URO induced natriuresis and diuresis, which were twice as large as those obtained with similar doses of ANP (Saxenhofer et al, 1990).…”

Urodilatin: a new approach for the treatment of therapy‐resistant acute renal failure after liver transplantation

“…With respect to this effect the pathophysiological differences between URO and CDD/ANP-99-126 are of interest [34]. Data suggest that URO is a more potent natriuretic agent than CDD/ANP-99-126 in vivo [28,35,36]. The mechanisms underlying this strong natriuretic potency in the kidney have not yet been clarified.…”

Urodilatin (Ularitide, INN): A Renal Natriuretic Peptide

“…Abassi et al [56.101] found URO to more effectively induce diure sis and natriuresis at equimolar concentrations ofURO and CDD/ANP-99-126. Rieggeret al [102] observed in experi mentally cardiomyopathic dogs with low-output heart fail ure that URO. but not A-type NP.…”