Preserved vasodilator effect of bradykinin in dogs with heart failure

Citation
Jb. Su et al., Preserved vasodilator effect of bradykinin in dogs with heart failure, CIRCULATION, 98(25), 1998, pp. 2911-2918
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
98
Issue
25
Year of publication
1998
Pages
2911 - 2918
Database
ISI
SICI code
0009-7322(199812)98:25<2911:PVEOBI>2.0.ZU;2-3
Abstract
Background-In heart failure (HF), vasoconstrictor systems are activated and endothelium-derived vasodilation is blunted. Bradykinin, a potent vasodila tor, may play an important role in this setting. However, it is not known w hether its vasodilator effect is modified in HF. Methods and 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 w as significantly blunted in HF. In contrast, in both control and HF, bradyk inin 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 ang iotensin 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 produ ce 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 pretreat ment with Hoe 140 (a bradykinin B-2 receptor antagonist). In contrast, in H F, vasodilator effects of ciprokiren were observed, but enalaprilat produce d larger changes in MAP and CO, and after Hoe 140, the hemodynamic effects of enalaprilat were significantly decreased, showing the effects of endogen ous bradykinin, which were similar to those measured in control. Conclusions-In this model of HF with a blunted endothelium-derived vasodila tion, the vasodilator effects of exogenous and endogenous bradykinin are pr eserved. These results suggest that bradykinin may play an important role i n HF, in which vasoconstriction is present and endothelium-dependent vasodi lation is blunted.