Effects of early perturbation of the renin-angiotensin system on cardiovascular remodeling in spontaneously hypertensive rats

Rationale: The goal of this study was to analyze cardiovascular (CV) remodeling in early, short-term CAP treated SHR and their offspring. Methods: We treated SHR with Captopril (CAP, 100 mg/kg) from in utero to 1 month of age (OCAP). Some of these rats were mated at 3-4 months of age and we used their offspring (2nd G). Controls were untreated SHR, normotensive Wistar Kyoto rats (WKY) and SHR maintained on CAP (SCAP). At 12-14 months of age, rats were cannulated for mean arterial blood pressure (MAP) measurements. An image analysis system was used to quantitate changes in cardiac and vascular (wall-to-lumen ratios, w/1) morphology and fibrosis. Results: Early, short-term CAP treatment prevented the full expression of hypertension in treated rats and their offspring. MAN were: SHR (180 +/- 2.2 nun Hg); WKY 125 3 min Hg); SCAP 112 +/- 2.5mm. Hg; OCAP 138 +/- 2.3 mm Hg; and 2nd G (145 +/- 2.0 nun Hg). There were significant decreases in heart weight/body weight ratios, large and small vessel morphology, and interstitial and perivascular fibrosis in CAP-treated animals and their offspring in comparison to untreated SHR. Conclusions: The CV protective properties of early, short-term CAP treatment were not solely due to a reduction in MAP. Although MAP was higher in OCAP and 2nd G, CV structure resembled that found in WKY and SCAR The effects of our early treatment appear to be due to chronic blockade of the renin-angiotensin system and its effects on growth of CV tissues and the development of fibrosis. (c) 2005 Published by Elsevier Inc.