Effects of early perturbation of the renin-angiotensin system on cardiovascular remodeling in spontaneously hypertensive rats.
BACKGROUND
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/l) morphology and fibrosis.


RESULTS
Early, short-term CAP treatment prevented the full expression of hypertension in treated rats and their offspring. MAPs were: SHR (180+/-2.2 mm Hg); WKY 125+/-3 mm Hg); SCAP 112+/-2.5mm Hg; OCAP 138+/-2.3 mm Hg; and 2nd G (145+/-2.0 mm 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 SCAP. 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.
Berecek
Kathleen H
KH
Department of Physiology and Biophysics, University of Alabama at Birmingham, 1530, 3rd Avenue South, MCLM 988, Birmingham, AL 35294, USA. Berecek@uab.edu
Reaves
Phyllis
P
Raizada
Mohan
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D002216:Captopril