Early captopril treatment prevents hypertrophydependent 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 hypertrophy. Blood pressures and hypertrophy are reduced in these animals (vs. untreated SHR) for up to 24 wk after discontinuation of the drug. We used conventional blot hybridization and Western analysis to examine hypertrophy-dependent gene expression during this period. Ventricular expression of the atrial natriuretic peptide gene was reduced by >90% at 16 wk of age in the captopril-treated SHR. Expression increased 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 expression of the atrial natriuretic peptide gene nor ventricular expression of the c-fos gene was affected by captopril. This study demonstrates that captopril treatment during a critical period of development in the SHR leads to a sustained reduction in hypertrophy-dependent myocardial gene expression, which does not revert to levels seen in the untreated SHR after discontinuation of the drug.
Chen
S
S
Metabolic Research Unit and Department of Medicine, University of California at San Francisco, San Francisco, California 94143, USA.
Su
J
J
Wu
K
K
Hu
W
W
Gardner
D G
DG
Chen
D
D
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002216:Captopril / Q000494:pharmacology*; D006332:Cardiomegaly / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006321:Heart / Q000503:physiopathology*; D006973:Hypertension / Q000235:genetics*; D007668:Kidney / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D011921:Rats, Inbred WKY; D013997:Time Factors; D016276:Ventricular Function / Q000502:physiology
D000959:Antihypertensive Agents; D009320:Atrial Natriuretic Factor; D002216:Captopril