EARLY CAPTOPRIL TREATMENT PREVENTS HYPERTROPHY-DEPENDENT GENE-EXPRESSION IN HEARTS OF SHR

Treatment of spontaneously hypertensive rats (SHR) with captopril (100 mg.kg(-1).day(-1)) throughout development and during the first 16 wk of life leads to a reduction in blood pressure and left ventricular hy pertrophy. Blood pressures and hypertrophy are reduced in these animal s (vs. untreated SHR) for up to 24 wk after discontinuation of the dru g. We used conventional blot hybridization and Western analysis to exa mine hypertrophy-dependent gene expression during this period. Ventric ular expression of the atrial natriuretic peptide gene was reduced by > 90% at 16 wk of age in the captopril-treated SHR. Expression increas ed in the 24 wk after discontinuation of treatment, but remained well below that of the untreated SHR. A similar reduction in ventricular c- myc gene expression was seen with captopril treatment. Neither renal e xpression of the atrial natriuretic peptide gene nor ventricular expre ssion of the c-fos gene was affected by captopril. This study demonstr ates that captopril treatment during a critical period of development in the SHR leads to a sustained reduction in hypertrophy-dependent myo cardial gene expression, which does not revert to levels seen in the u ntreated SHR after discontinuation of the drug.