Captopril restores hemodynamic responsiveness to atrial natriuretic peptide in rats with heart failure

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 μg/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. In rats with heart failure that were pretreated with captopril, infusion of atrial natriuretic peptide produced significant hemodynamic effects. Left ventricular end-diastolic pressure, mean aortic pressure, and mean circulatory filling pressure decreased from 14 ± 2 to 10 ± 2 mm Hg, from 84 ± 5 to 73 ± 6 mm Hg, and from 8.0 ± 1.4 to 7.0 ± 1.2 mm Hg, respectively. Captopril and atrial natriuretic peptide increased heart rate; right atrial pressure was unchanged. Captopril and atrial natriuretic peptide normalized total blood volume from 60.5 ± 1.1 to 54.3 ± 1.0 ml/kg. In summary, captopril restored the responsiveness to atrial natriuretic peptide in rats with heart failure. In particular, left ventricular end-diastolic pressure decreased toward normal, and total blood volume was normalized.