Bradykinin pathway is involved in acute hemodynamic effects of enalaprilat in dogs with heart failure.

Abstract

To determine the role of the renin-angiotensin system and the bradykinin pathway in the mechanism of action of angiotensin-converting enzyme inhibitors in heart failure, the acute effects of enalaprilat (1 mg/kg) were compared with those of a renin inhibitor (ciprokiren, 1 mg/kg i.v.) in 10 chronically instrumented conscious dogs with heart failure induced by right ventricular pacing (3 wk, 240 beats/min). The effects of enalaprilat and ciprokiren on bradykinin infusion (3, 10, and 30 micrograms/min) and the effects of enalaprilat in the presence of the bradykinin B2 receptor antagonist Hoe-140 (10 micrograms/kg i.v.) were also examined. Both inhibitors significantly decreased mean aortic pressure and increased cardiac output. However, enalaprilat induced significantly greater hemodynamic effects than ciprokiren (mean aortic pressure, -13 +/- 3 vs. -6 +/- 1 mmHg; cardiac output, 0.4 +/- 0.1 vs. 0.15 +/- 0.1 l/min). Bradykinin infusion led to dose-dependent decreases in mean aortic pressure and increases in cardiac output that were not modified by pretreatment with ciprokiren but were potentiated 10-fold by enalaprilat. Hoe-140 significantly reduced the hemodynamic effects of enalaprilat. Thus endogenous bradykinin is involved in the acute hemodynamic effects of enalaprilat in experimental heart failure.

• Authors: F Barbe, J B Su, T T Guyene, B Crozatier, J Ménard, L Hittinger
• Journal: The American journal of physiology (Am J Physiol) Vol. 270 Issue 6 Pt 2 Pg. H1985-92 (Jun 1996) ISSN: 0002-9513 [Print] United States
• PMID: 8764248 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Bradykinin Receptor Antagonists
• Hormones
• Imidazoles
• ciprokiren
• icatibant
• Renin
• Enalaprilat
• Bradykinin

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Bradykinin (analogs & derivatives, metabolism, pharmacology, physiology)
• Bradykinin Receptor Antagonists
• Cardiac Output, Low (blood, physiopathology)
• Dogs
• Enalaprilat (pharmacology)
• Female
• Hemodynamics (drug effects, physiology)
• Hormones (blood)
• Imidazoles (pharmacology)
• Male
• Renin (antagonists & inhibitors)
• Time Factors