Vasopeptidase inhibitors: A new therapeutic concept in cardiovascular disease?

Roberto Corti, John C Jr. Burnett, Jean L. Rouleau, Frank Ruschitzka, Thomas F. Lüscher

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

The cardiovascular system is regulated by hemodynamic and neurohumoral mechanisms. These regulatory systems play a key role in modulating cardiac function, vascular tone, and structure. Although neurohumoral systems are essential in vascular homeostasis, they become maladaptive in disease states such as hypertension, coronary disease, and heart failure. The clinical success of ACE inhibitors has led to efforts to block other humoral systems. Neutral endopeptidase (NEP) is an endothelial cell surface zinc metallopeptidase with similar structure and catalytic site. NEP is the major enzymatic pathway for degradation of natriuretic peptides, a secondary enzymatic pathway for degradation of kinins, and adrenomedullin. The natriuretic peptides can be viewed as endogenous inhibitors of the renin angiotensin system. Inhibition of NEP increases levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) of myocardial cell origin, and C-type natriuretic peptide (CNP) of endothelial cell origin as well as bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide and kinin systems, vasopeptidase inhibitors reduce vasoconstriction, enhance vasodilation, improve sodium/water balance, and, in turn, decrease peripheral vascular resistance and blood pressure and improve local blood flow. Within the blood vessel wall, this leads to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II and increased local levels of bradykinin (and, in turn, nitric oxide) and natriuretic peptides. Preliminary clinical experiences with vasopeptidase inhibitors are encouraging. Thus, the combined inhibition of ACE and neutral endopeptidase is a new and promising approach to treat patients with hypertension, atherosclerosis, or heart failure.

Original languageEnglish (US)
Pages (from-to)1856-1862
Number of pages7
JournalCirculation
Volume104
Issue number15
StatePublished - Oct 9 2001

Fingerprint

Neprilysin
Natriuretic Peptides
Cardiovascular Diseases
Adrenomedullin
Blood Vessels
bradykinin potentiating factors
Bradykinin
Renin-Angiotensin System
Vascular Resistance
Endothelial Cells
Heart Failure
C-Type Natriuretic Peptide
Hypertension
Kinins
Brain Natriuretic Peptide
Metalloproteases
Atrial Natriuretic Factor
Vasoconstrictor Agents
Therapeutics
Cardiovascular System

Keywords

  • Heart failure
  • Hypertension
  • Treatment

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Corti, R., Burnett, J. C. J., Rouleau, J. L., Ruschitzka, F., & Lüscher, T. F. (2001). Vasopeptidase inhibitors: A new therapeutic concept in cardiovascular disease? Circulation, 104(15), 1856-1862.

Vasopeptidase inhibitors : A new therapeutic concept in cardiovascular disease? / Corti, Roberto; Burnett, John C Jr.; Rouleau, Jean L.; Ruschitzka, Frank; Lüscher, Thomas F.

In: Circulation, Vol. 104, No. 15, 09.10.2001, p. 1856-1862.

Research output: Contribution to journalArticle

Corti, R, Burnett, JCJ, Rouleau, JL, Ruschitzka, F & Lüscher, TF 2001, 'Vasopeptidase inhibitors: A new therapeutic concept in cardiovascular disease?', Circulation, vol. 104, no. 15, pp. 1856-1862.
Corti R, Burnett JCJ, Rouleau JL, Ruschitzka F, Lüscher TF. Vasopeptidase inhibitors: A new therapeutic concept in cardiovascular disease? Circulation. 2001 Oct 9;104(15):1856-1862.
Corti, Roberto ; Burnett, John C Jr. ; Rouleau, Jean L. ; Ruschitzka, Frank ; Lüscher, Thomas F. / Vasopeptidase inhibitors : A new therapeutic concept in cardiovascular disease?. In: Circulation. 2001 ; Vol. 104, No. 15. pp. 1856-1862.
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