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Captopril restores hemodynamic responsiveness to atrial natriuretic peptide in rats with heart failure
T E Raya1, R W Lee, T Westhoff
1Department of Internal Medicine, Tucson Veterans Administration Medical Center, AZ 85723.
Insights
Captopril treatment improved heart function in rats with heart failure, restoring responsiveness to atrial natriuretic peptide. This suggests captopril may enhance atrial natriuretic peptide therapy for heart failure patients.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Atrial natriuretic peptide (ANP) levels are elevated in heart failure.
- Hemodynamic responses to exogenous ANP are blunted in heart failure.
- Captopril is an angiotensin-converting enzyme inhibitor.
Purpose of the Study:
- To determine if captopril can restore hemodynamic responsiveness to ANP infusion in rats with heart failure.
- To investigate the effects of captopril and ANP on hemodynamic parameters in a rat model of heart failure.
Main Methods:
- A rat model of heart failure was created using coronary artery ligation.
- Rats with heart failure received either captopril or placebo for 4 weeks.
- Following treatment, rats received an infusion of ANP (0.3 microgram/kg/min).
Main Results:
- Captopril treatment alone improved hemodynamics, decreasing left ventricular end-diastolic pressure, mean aortic pressure, and mean circulatory filling pressure.
- Captopril treatment increased venous compliance and decreased total blood volume.
- ANP infusion alone had minimal hemodynamic effects but increased venous compliance and heart rate in rats with heart failure.
Conclusions:
- Captopril treatment alone improved hemodynamic parameters in rats with heart failure.
- Captopril treatment appears to restore hemodynamic responsiveness to ANP infusion in this heart failure model.
- These findings suggest a potential therapeutic synergy between captopril and ANP in managing heart failure.
Abstract:
Atrial natriuretic peptide levels are elevated in heart failure. However, the hemodynamic responses to exogenous atrial natriuretic peptide infusion in heart failure are blunted. To determine if captopril can restore hemodynamic responsiveness to atrial natriuretic peptide infusion in rats with heart failure, studies were performed in a rat model of heart failure after coronary artery ligation. Rats with heart failure received either captopril (2 g/l drinking water) or placebo for 4 weeks and then were treated with an infusion of atrial natriuretic peptide (0.3 microgram/kg/min). Captopril treatment alone improved hemodynamics. Left ventricular end-diastolic pressure, mean aortic pressure, and mean circulatory filling pressure decreased from 22 +/- 2 to 14 +/- 1, from 106 +/- 4 to 76 +/- 3, and from 10.5 +/- 0.6 to 8.8 +/- 0.4 mm Hg, respectively. Heart rate, right atrial pressure, and hematocrit were unchanged. Total blood volume decreased from 66.0 +/- 1.0 to 60.0 +/- 1.0 ml/kg; venous compliance increased from 2.1 +/- 0.1 to 2.7 +/- 0.1 ml/kg/mm Hg. Atrial natriuretic peptide alone had minimal hemodynamic effects on rats with heart failure. There was no change in right atrial pressure, mean aortic pressure, left ventricular end-diastolic pressure, mean circulatory filling pressure, and total blood volume. However, atrial natriuretic peptide infusion increased venous compliance from 2.1 +/- 0.1 to 2.4 +/- 0.1 ml/kg/mm Hg. Heart rate and hematocrit increased from 323 +/- 5 to 359 +/- 8 beats/min and from 48 +/- 1% to 51 +/- 1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)