ENALAPRIL AND LOSARTAN REDUCED CARDIAC MASS AND IMPROVED CORONARY HEMODYNAMICS IN SHR

Among the multiple mechanisms postulated for the increased risk of hyp ertensive left ventricular hypertrophy (LVH), coronary hemodynamic alt erations remain a strong possibility. This study was designed to compa re the effects of treatment with an ACE inhibitor (enalapril) and an a ngiotensin ATI receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two re nin-angiotensin system (RAS) inhibitors would be as or more effective in reducing mean arterial pressure (MAP), left ventricular (LV) mass, and improving coronary hemodynamics than either regimen alone. Thus, 2 3 week old spontaneously hypertensive rats (SHR) were treated (12 week s) with tap water (C), enalapril (30 mg . kg(-1). d(-1)), losartan (30 mg . kg(-1). d(-1)), or their combination (15 mg . k(-1). d(-1)). Age -matched Wistar-Kyoto (WKY) rats served as normotensive controls. Afte r 12 weeks, systemic and coronary hemodynamics were determined (15 mu m radiolabeled microspheres) at baseline, during maximal treadmill exe rcise, and during maximal dilation (dipyridamole). Enalapril and losar tan equally reduced MAP and LV mass in association with a decreased to tal peripheral resistance, The RAS combination reduced MAP and LV mass more than either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit of LV mass did not differ among the groups. Altho ugh enalapril did not improve coronary how reserve (CFR), it diminishe d minimal coronary vascular resistance (MCVR); losartan improved both. However, the combination was more effective than either agent alone, reaching values close to normotensive WKY controls. in conclusion, the se data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapri l improved systemic and coronary hemodynamics more than enalapril alon e.