Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

Abstract

Angiotensin-converting enzyme inhibitors reduce blood pressure and attenuate cardiac and vascular remodeling in hypertension. However, the kinetics of remodeling after discontinuation of the long-term use of these drugs are unknown. Our objective was to investigate the temporal changes occurring in blood pressure and vascular structure of spontaneously hypertensive rats (SHR). Captopril treatment was started in the pre-hypertensive state. Rats (4 weeks) were assigned to three groups: SHR-Cap (N = 51) treated with captopril (1 g/L) in drinking water from the 4th to the 14th week; SHR-C (N = 48) untreated SHR; Wistar (N = 47) control rats. Subgroups of animals were studied at 2, 4, and 8 weeks after discontinuation of captopril. Direct blood pressure was recorded in freely moving animals after femoral artery catheterism. The animals were then killed to determine left ventricular hypertrophy (LVH) and the aorta fixed at the same pressure measured in vivo. Captopril prevented hypertension (105 ± 3 vs 136 ± 5 mmHg), LVH (2.17 ± 0.05 vs 2.97 ± 0.14 mg/g body weight) and the increase in cross-sectional area to luminal area ratio of the aorta (0.21 ± 0.01 vs 0.26 ± 0.02 μm²) (SHR-Cap vs SHR-C). However, these parameters increased progressively after discontinuation of captopril (22nd week: 141 ± 2 mmHg, 2.50 ± 0.06 mg/g, 0.27 ± 0.02 μm²). Prevention of the development of hypertension in SHR by using captopril during the prehypertensive period prevents the development of cardiac and vascular remodeling. Recovery of these processes follows the kinetic of hypertension development after discontinuation of captopril.

Keywords

• SHR
• Cardiac hypertrophy
• Aorta remodeling
• ACE inhibition
• Captopril