Emerging concepts of neurohumoral modulation in the treatment of congestive heart failure.
The angiotensin converting enzyme (ACE), endothelin (ET) converting enzyme (ECE) and neutral endopeptidase (NEP) are all zinc-metallopeptidases expressed in almost all the organs, such as heart, vessels and kidneys. While ACE and ECE are respectively involved in the transformation of angiotensin I and Big-ET into angiotensin II and ET-1 respectively, which possess vasoconstrictor and mitogenic properties, NEP is involved in the degradation of atrial natriuric factor (ANF), which possesses vasorelaxant, diuretic/natriuretic and antihypertrophic properties. These three systems are activated in heart failure and modulate the progression of heart failure. This article will discuss preliminary date concerning simultaneous inhibition of ACE, ECE and/or NEP and their therapeutic potential interest in the treatment of heart failure.
Mulder
P
P
INSERM E9920, IFRMP No. 23, Rouen University Medical School, France. paul.mulder@univ-rouen.fr
Thuillez
Ch
Ch
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016282:Aspartic Acid Endopeptidases / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D000072396:Endothelin-Converting Enzymes; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008666:Metalloendopeptidases / Q000494:pharmacology / Q000627:therapeutic use; D015260:Neprilysin / Q000494:pharmacology* / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D000072396:Endothelin-Converting Enzymes