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Enalapril and losartan reduced cardiac mass and improved coronary hemodynamics in SHR
1Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, La 70121, USA.
Insights
Losartan, alone or combined with enalapril, improved coronary hemodynamics in hypertensive rats more effectively than enalapril alone, reducing blood pressure and left ventricular mass.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Hypertension Research
Background:
- Hypertensive left ventricular hypertrophy (LVH) is linked to coronary hemodynamic alterations.
- The renin-angiotensin system (RAS) plays a key role in regulating blood pressure and cardiac structure.
Purpose of the Study:
- To compare the effects of enalapril (ACE inhibitor) and losartan (AT1 receptor antagonist) on systemic and coronary hemodynamics in spontaneously hypertensive rats (SHR).
- To evaluate the efficacy of combining enalapril and losartan in reducing blood pressure, LV mass, and improving coronary hemodynamics compared to monotherapy.
Main Methods:
- Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls were treated for 12 weeks with enalapril, losartan, their combination, or water.
- Systemic and coronary hemodynamics were assessed using radiolabeled microspheres during rest, exercise, and pharmacologic vasodilation (dipyridamole).
Main Results:
- Both enalapril and losartan reduced mean arterial pressure (MAP) and left ventricular (LV) mass, decreasing total peripheral resistance.
- The combination therapy showed greater reductions in MAP and LV mass than either agent alone.
- Losartan, and the combination therapy, improved coronary flow reserve (CFR) and diminished minimal coronary vascular resistance (MCVR), with the combination approaching normotensive control values.
Conclusions:
- Untreated SHR exhibit impaired coronary blood flow (CBF), CFR, and MCVR.
- Losartan, either alone or combined with enalapril, offers superior improvement in systemic and coronary hemodynamics compared to enalapril monotherapy in hypertensive rats.
Abstract:
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) inhibitor 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 their 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 microns 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.