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Functional effects of endogenous bradykinin in congestive heart failure
1Cardiology Section, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1045, USA. ccheng@bgsm.edu
Insights
Endogenous bradykinin dilates coronary arteries before congestive heart failure (CHF) but has no systemic effects. In CHF, bradykinin levels rise, improving cardiovascular function through vasodilation and enhanced cardiac performance.
Area of Science:
- Cardiovascular Physiology
- Renin-Angiotensin-Aldosterone System (RAAS) Modulation
- Pharmacology of Kinins
Background:
- Bradykinin levels are elevated in certain cardiac diseases.
- Plasma bradykinin levels in congestive heart failure (CHF) remain uncharacterized.
- Cardiac and vascular responses to bradykinin in CHF are not well understood.
Purpose of the Study:
- To quantify endogenous bradykinin levels in CHF.
- To investigate the functional effects of bradykinin on cardiovascular parameters in CHF.
- To elucidate the role of bradykinin in preserving cardiac function during CHF.
Main Methods:
- Assessed circulating bradykinin levels and functional effects in eight conscious dogs.
- Induced congestive heart failure (CHF) using a pacing model.
- Utilized HOE-140, a specific bradykinin B2-receptor antagonist, to block endogenous bradykinin.
Main Results:
- Before CHF, bradykinin blockade reduced coronary blood flow but did not affect systemic hemodynamics or cardiac contractility.
- After CHF induction, plasma bradykinin levels significantly increased.
- In CHF, bradykinin blockade worsened cardiac function, decreasing coronary blood flow, increasing systemic vascular resistance, and impairing left ventricular relaxation and contractility.
Conclusions:
- Endogenous bradykinin causes coronary vasodilation without systemic effects before CHF.
- In CHF, significantly elevated bradykinin acts via B2-receptors to promote coronary and arterial vasodilation, improving left ventricular relaxation and contractility.
- Bradykinin plays a crucial role in maintaining cardiovascular homeostasis in the setting of CHF.
Objectives:
The purpose of this study was to determine the level and functional effects of endogenous bradykinin in congestive heart failure (CHF).
Background:
There is experimental evidence that bradykinin is increased in several cardiac disease states. However, it is unknown whether plasma levels of bradykinin are elevated in CHF. Further, the cardiac and vascular responses to bradykinin in CHF are unclear.
Methods:
The circulating levels of bradykinin and the effects of endogenous bradykinin were assessed in eight instrumented, conscious dogs both before and after pacing-induced CHF.
Results:
Before CHF, the plasma bradykinin level was 53.1 +/- 12.4 pg/ml. Blocking endogenous bradykinin with HOE-140 (0.3 mg/kg), a specific bradykinin B2-receptor antagonist, produced no significant alterations in heart rate, left ventricular (LV) end-systolic pressure (Pes), total systemic resistance (TSR), the time constant of LV relaxation (tau) or the maximal rate of LV filling (dV/dt(max)). However, coronary blood flow was significantly reduced (p < 0.05). LV contractile performance measured by the slopes of pressure-volume relations was unaffected. After induction of CHF, the plasma bradykinin level increased to 234.2 +/- 19.4 pg/ml (p < 0.05). Blocking endogenous bradykinin with HOE-140 reduced coronary blood flow and produced significant increases in Pes and TSR, prolonged tau, decreased dV/dt(max) and elevated minimal LV pressure and mean left atrial pressure. Furthermore, the slopes of pressure-volume relations (p < 0.05) were decreased, indicating depressed contractility with HOE-140 after CHF.
Conclusions:
Before CHF, endogenous bradykinin results in coronary dilation but has no effect on systemic arterial vasodilation or cardiac performance. After CHF, endogenous bradykinin is significantly increased and, acting through B2-receptors, produces coronary and arterial vasodilation and improves LV relaxation and contractile performance. Thus, endogenous bradykinin may play an important role in preserving cardiovascular function in CHF.
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