title: Importance of endogenous compensatory vasoactive peptides in broadening the effects of inhibitors of the renin-angiotensin system for the treatment of heart failure.
abstract: The magnitude of the clinical benefits produced by inhibitors of the renin-angiotensin system in heart failure has been modest, possibly because of the ability of renin-angiotensin activity to escape from suppression during long-term treatment. Efforts to intensify pharmacological blockade by use of dual inhibitors that interfere with the renin-angiotensin system at multiple sites have not yielded consistent incremental clinical benefits, but have been associated with serious adverse reactions. By contrast, potentiation of endogenous compensatory vasoactive peptides can act to enhance the survival effects of inhibitors of the renin-angiotensin system, as evidenced by trials that have compared angiotensin-converting enzyme inhibitors with drugs that inhibit both the renin-angiotensin system and neprilysin. Several endogenous vasoactive peptides act as adaptive mechanisms, and their augmentation could help to broaden the benefits of renin-angiotensin system inhibitors for patients with heart failure.
authors.affiliation: Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA. Electronic address: milton.packer@baylorhealth.edu.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: British Heart Foundation Cardiovascular Research Center, University of Glasgow, Glasgow, UK.
authors.forename: John J V
authors.initials: JJV
authors.lastname: McMurray
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors; D009479:Neuropeptides / Q000502:physiology*; D036361:Peptide Hormones / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000075563:Vasopeptidase Inhibitors / Q000627:therapeutic use
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D009479:Neuropeptides; D036361:Peptide Hormones; D011453:Prostaglandins; D000075563:Vasopeptidase Inhibitors; D015260:Neprilysin