Bradykinin pathway is involved in acute hemodynamic effects of enalaprilat in dogs with heart failure.
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.
Barbe
F
F
Institut National de la santé et de la Recherche Médicale, Faculté de Médecine, Créteil, France.
Su
J B
JB
Guyene
T T
TT
Crozatier
B
B
Ménard
J
J
Hittinger
L
L
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D065168:Bradykinin Receptor Antagonists; D002303:Cardiac Output, Low / Q000097:blood / Q000503:physiopathology*; D004285:Dogs; D015773:Enalaprilat / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006728:Hormones / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D013997:Time Factors; D000092502:Renin Inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001920:Bradykinin; D065168:Bradykinin Receptor Antagonists; D015773:Enalaprilat; D006728:Hormones; D007093:Imidazoles; D000092502:Renin Inhibitors; C085570:ciprokiren; C065679:icatibant