Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on pulmonary pressures in congestive heart failure.
SLV306, a potent neutral endopeptidase (NEP) inhibitor with additional endothelin-converting enzyme (ECE)-inhibitory activity, in doses of 200, 400, and 800 mg reduced pulmonary and right atrial pressures, although there was not a clear dose response. Systemic blood pressure, heart rate, and cardiac output were unaffected. SLV306 increased plasma natriuretic peptides and big endothelin-1 levels in a dose-dependent manner, confirming NEP and ECE inhibition. The combined inhibition of NEP and ECE may be useful in heart failure by reducing right and left cardiac filling pressures.
Dickstein
Kenneth
K
University of Bergen, Central Hospital Rogaland, Stavanger, Norway. kenneth.dickstein@med.uib.no
De Voogd
Hanka J
HJ
Miric
Milutin P
MP
Willenbrock
Roland
R
Mitrovic
Veselin
V
Pacher
Richard
R
Koopman
Paul A
PA
D000368:Aged; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001552:Benzazepines / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D000072396:Endothelin-Converting Enzymes; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011651:Pulmonary Artery / Q000502:physiology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects*
D001552:Benzazepines; C405520:SLV 306; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D000072396:Endothelin-Converting Enzymes