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(Hypertension. 1997;29:519.)
© 1997 American Heart Association, Inc.
State-of-the-Art-Lecture |
Enalapril and Losartan Reduced Cardiac Mass and Improved Coronary Hemodynamics in SHR
From Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, LA.
Correspondence to Edward D. Frohlich, MD, Vice President for Academic Affairs, Alton Ochsner Medical Foundation, 1516 Jefferson Hwy, New Orleans, LA 70121
Among the multiple mechanisms postulated for the increased risk of hypertensive left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a strong possibility. This study was designed to compare the effects of treatment with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two renin-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, 23 week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap water (C), enalapril (30 mg·kg-1· d-1), losartan (30 mg·kg-1·d-1), or combination (15 mg·kg-1 ·d-1). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls. After 12 weeks, systemic and coronary hemodynamics were determined (15 µm radiolabeled microspheres) at baseline, during maximal treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and losartan equally reduced MAP and LV mass in association with a decreased total 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. Although enalapril did not improve coronary flow reserve (CFR), it diminished 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, these data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapril improved systemic and coronary hemodynamics more than enalapril alone.
Key Words: left ventricular hypertrophy [reversal] • angiotensin II [antagonism and inhibition] • drug synergism • losartan • enalapril • coronary circulation • spontaneously hypertensive rats
Abbreviations: CBF = coronary blood flow • CFR = coronary flow reserve • CO = cardiac output • CVR = coronary vascular resistance • CVRI = coronary vascular resistance index • LV = left ventricular/ventricle • LVH = LV hypertrophy • MAP = mean arterial pressure • MCVR = minimal coronary vascular resistance • RV = right ventricular/ventricle • SHR = spontaneously hypertensive rats • SHR-C = SHR controls • SHR-E = enalapril-treated controls • SHR-E&L = combination-treated controls • SHR-L = losartan-treated controls • TPRI = total peripheral resistance index • WKY = Wistar-Kyoto • WKY-C = WKY controls
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