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

Objective To determine whether antihypertensive treatment could alter hyper tension 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 differe ntiate between hypertension and age-related changes, a comparison was made between left and right ventricular indices since the right ventricle was no t 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 an d coronary hemodynamics (radionuclide-labelled microspheres), right and lef t ventricular and aortic mass indices, and right and left ventricular hydro xyproline concentrations (an estimate of collagen) were determined. Results Arterial pressure and total peripheral resistance were reduced to t he same extent in SHRs treated with either felodipine or enalapril; however , compared to the control rats, enalapril was more effective in reducing le ft ventricular and aortic mass indices. Both agents also improved coronary hemodynamics of both ventricles in aged SHR but enalapril was more effectiv e as indicated by a greater increase in coronary flow reserve and a greater decrease in minimal coronary vascular resistance. Furthermore, enalapril b ut not felodipine reduced left ventricular hydroxyproline concentration; an d right ventricular hydroxyproline concentration increased with felodipine but remained unchanged with enalapril, Conclusions Both enalapril and felodipine ameliorated adverse cardiovascula r effects of hypertension in the aged SHRs within 12 weeks, as demonstrated by reduced arterial pressure, diminished left ventricular mass, and improv ed coronary hemodynamics, Enalapril also decreased aortic mass and left ven tricular collagen concentration and appeared to be more effective in improv ing coronary hemodynamics than felodipine, possibly as a result, in part, o f reduced myocardial fibrosis, J Hypertens 1999, 17:1209-1215 (C) Lippincot t Williams & Wilkins.