Pharmacologic agents on cardiovascular mass, coronary dynamics and collagen in aged spontaneously hypertensive rats

Abstract

Objective: To determine whether antihypertensive treatment could alter hypertension and age-related progressive impairment of coronary hemodynamics and cardiac fibrosis in aged spontaneously hypertensive rats (SHR).

Design: Old SHR were given their respective therapy for 3 months. To differentiate between hypertension and age-related changes, a comparison was made between left and right ventricular indices since the right ventricle was not exposed to pressure overload.

Methods: Male, 65-week-old spontaneously SHR were divided into three groups and were given either vehicle, felodipine (30 mg/kg per day) or enalapril (30 mg/kg per day). After 12 weeks of the respective treatments, systemic and coronary hemodynamics (radionuclide-labelled microspheres), right and left ventricular and aortic mass indices, and right and left ventricular hydroxyproline concentrations (an estimate of collagen) were determined.

Results: Arterial pressure and total peripheral resistance were reduced to the same extent in SHRs treated with either felodipine or enalapril; however, compared to the control rats, enalapril was more effective in reducing left ventricular and aortic mass indices. Both agents also improved coronary hemodynamics of both ventricles in aged SHR but enalapril was more effective as indicated by a greater increase in coronary flow reserve and a greater decrease in minimal coronary vascular resistance. Furthermore, enalapril but not felodipine reduced left ventricular hydroxyproline concentration; and right ventricular hydroxyproline concentration increased with felodipine but remained unchanged with enalapril.

Conclusions: Both enalapril and felodipine ameliorated adverse cardiovascular effects of hypertension in the aged SHRs within 12 weeks, as demonstrated by reduced arterial pressure, diminished left ventricular mass, and improved coronary hemodynamics. Enalapril also decreased aortic mass and left ventricular collagen concentration and appeared to be more effective in improving coronary hemodynamics than felodipine, possibly as a result, in part, of reduced myocardial fibrosis.