Prevention of the development of heart failure and the regression of cardiac hypertrophy by captopril in the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) exhibits both a compensated phase of cardiac hypertrophy in which forward output is maintained despite persistently elevated systemic arterial pressures and a decompensated phase in which cardiac performance has deteriorated in spite of further hypertrophic growth. To determine whether chronic antihypertensive therapy prevents the development of heart failure and the progression of cardiac hypertrophy in SHR with advanced hypertension, captopril (2 g/l of drinking water), a converting enzyme inhibitor, was administered to 14 month old female SHR and normotensive American Wistar rats (NWR) for 10 months. The severe left ventricular hypertrophy of the 24 month old untreated SHR (4.37 +/- 0.2 mg/g v. 2.50 +/- 0.06 mg/g, untreated NWR) was markedly reduced (P less than 0.02) by captopril (3.01 +/- 0.1 mg/g). Chronic therapy prevented the reduction of both baseline and maximal cardiac indices in SHR, but did not alter blood flow in NWR. Left ventricular dilatation was present in 24 month old SHR and, as peak stroke volume index was diminished, the ejection fraction index of the SHR was reduced. Captopril restored this index in SHR to normal. The relation of ejection fraction index and afterload (peak systolic wall stress) was depressed in untreated SHR, but was normal in treated SHR. Thus, chronic therapy with captopril prevented the development of severe cardiac dysfunction and produced a marked regression of cardiac hypertrophy in SHR with advanced hypertensive heart disease.