Role of the natriuretic peptides in the cardiorenal and humoral actions of omapatrilat: insights from experimental heart failure.
Vasopeptidase (VP) inhibitors are novel molecules that co-inhibit neutral endopeptidase 24.11 (NEP), which degrades natriuretic peptides and angiotensin-converting enzyme (ACE). We review the biology of the natriuretic peptide system and a recent study of the role for the natriuretic peptide system in the mechanism of action of omapatrilat (the most clinically advanced VP inhibitor). This study compared the cardiorenal and humoral actions of omapatrilat with those of ACE inhibition. The actions of omapatrilat were further defined in the presence and absence of a natriuretic peptide receptor antagonist. This investigation provided insight into a unique new pharmacologic agent that has beneficial renal actions in experimental mild heart failure that exceed those seen with ACE inhibition alone and that are linked to the natriuretic peptide system.
Chen
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HH
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Guggenheim 915, 200 First Street SW, Rochester, MN 55905, USA.
Cataliotti
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A
Burnett
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JC
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D013841:Thiazepines / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat; D009320:Atrial Natriuretic Factor; D015260:Neprilysin