Preserved vasodilator effect of bradykinin in dogs with heart failure.
BACKGROUND
In heart failure (HF), vasoconstrictor systems are activated and endothelium-derived vasodilation is blunted. Bradykinin, a potent vasodilator, may play an important role in this setting. However, it is not known whether its vasodilator effect is modified in HF.


RESULTS
Fourteen chronically instrumented dogs were studied in the control state and in pacing-induced HF (250 bpm for 3 weeks). The dose-dependent decrease in mean aortic pressure (MAP) induced by acetylcholine was significantly blunted in HF. In contrast, in both control and HF, bradykinin infusion caused similar dose-dependent decreases in MAP and increases in cardiac output (CO). This vasodilator effect of exogenous bradykinin was potentiated similarly in both states by enalaprilat, which blocks both angiotensin conversion and bradykinin degradation. For evaluating the role of endogenous bradykinin, the effects of enalaprilat were compared with those of ciprokiren, a pure renin inhibitor. In control, ciprokiren did not produce any effect. Enalaprilat, however, produced a significant decrease in MAP and a significant increase in CO, which were attributed to the inhibition of bradykinin degradation, because these effects were absent after pretreatment with Hoe 140 (a bradykinin B2 receptor antagonist). In contrast, in HF, vasodilator effects of ciprokiren were observed, but enalaprilat produced larger changes in MAP and CO, and after Hoe 140, the hemodynamic effects of enalaprilat were significantly decreased, showing the effects of endogenous bradykinin, which were similar to those measured in control.


CONCLUSIONS
In this model of HF with a blunted endothelium-derived vasodilation, the vasodilator effects of exogenous and endogenous bradykinin are preserved. These results suggest that bradykinin may play an important role in HF, in which vasoconstriction is present and endothelium-dependent vasodilation is blunted.
Su
J B
JB
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 400, Faculté de Médecine, Créteil, France. jbsu@im3.inserm.fr
Barbe
F
F
Houel
R
R
Guyene
T T
TT
Crozatier
B
B
Hittinger
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004285:Dogs; D015773:Enalaprilat / Q000494:pharmacology; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D065168:Bradykinin Receptor Antagonists; D014665:Vasodilator Agents; C065679:icatibant; D015773:Enalaprilat; D000109:Acetylcholine; D001920:Bradykinin