Effect of neutral endopeptidase inhibitor in rats with congestive heart failure.
1. The acute hormonal, renal and haemodynamic effects of SCH 39370, a new neutral endopeptidase (NEP) inhibitor, were evaluated in rats with congestive heart failure (CHF) produced by coronary ligation. 2. Left ventricular systolic pressure and left ventricular end diastolic pressure were significantly decreased by SCH 39370 treatment. 3. SCH 39370 improved cardiac function by increasing cardiac index and decreasing total peripheral resistance. 4. SCH 39370 induced a transient but significant diuresis and natriuresis. 5. These effects were associated with significant increases in urinary atrial natriuretic peptide (ANP) and cyclic GMP excretion, but not with an increase in plasma ANP levels. 6. The results suggest that NEP inhibition may be a new therapeutic method for treating CHF possibly by potentiating the biological activities of endogenous ANP.
Murohara
Y
Y
Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Victoria, Australia.
Johnston
C I
CI
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000652:urine; D002302:Cardiac Output / Q000187:drug effects; D006152:Cyclic GMP / Q000652:urine; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D004151:Dipeptides; D014677:Pharmaceutical Vehicles; D011480:Protease Inhibitors; C060631:Sch 39370; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP