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KMID : 1146920200500060573
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Journal of Pharmaceutical Investigation
2020 Volume.50 No. 6 p.573 ~ p.581
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The effects of combined treatment of losartan and ramipril on hypertension and related complications
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Park Hyun-Soo
Lee Do-Hyung
Han Joo-Hui
Jung Sang-Hyuk
Lee Mi-Ji
Jang Keun-Woo
Myung Chang-Seon
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Abstract
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Purpose: Polypharmacy has been an important strategy for the management of hypertension. The aim of this study was to investigate the effect of combined treatment of losartan with ramipril on hypertension, myocardial infarction and vascular remodeling in disease animal models.
Methods: In 8-telemetered spontaneous hypertensive rats (SHRs) orally treated with various doses of drugs or vehicle by cross-over protocol, systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were measured. The infarct size was measured in rats subjected to 30 min occlusion of the left anterior descending coronary artery (LAD) followed by 150 min reperfusion in myocardial ischemia/reperfusion (MI/R) rats injected drugs or vehicle once through femoral vein 15 min before inducing ischemia. The neointima formation and DNA synthesis in intima and media layer of the blood vessels were measured in cuff-induced vascular injury mice orally treated with drugs for 2 weeks.
Results: As compared with single treatment, the combination therapy of both drugs significantly decreased SBP and MAP without significant reflex tachycardia. The combined treatment of both drugs significantly increased the expression of endothelial nitric oxide synthase (eNOS) in coronary arterial tissues including area at occlusion. The combination therapy significantly decreased the thickness of vascular media layer and the number of bromodeoxyuridine (BrdU)-positive cells in both intima and media.
Conclusion: The present data suggest that the combination therapy with fixed doses of losartan and ramipril may exert greater BP-lowering effects with protection against myocardial infarction and vascular remodeling.
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KEYWORD
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Losartan, Ramipril, Combination therapy, Hypertension, Vascular remodeling
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