Effects of ANP-(95-126) in dogs before and after induction of heart failure.
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.
Riegger
G A
GA
Medizinische Universitätsklinik, Würzburg, Federal Republic of Germany.
Elsner
D
D
Forssmann
W G
WG
Kromer
E P
EP
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000652:urine; D002303:Cardiac Output, Low / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D006152:Cyclic GMP / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006728:Hormones / Q000097:blood; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000494:pharmacology* / Q000652:urine
D006728:Hormones; D010446:Peptide Fragments; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP