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The effects of combined treatment of losartan and ramipril on hypertension and related complications

Journal of Pharmaceutical Investigation 2020년 50권 6호 p.573 ~ 581
박현수, 이도형, Han Joo-Hui, 정상혁, 이미지, 장근우, 명창선,
소속 상세정보
박현수 ( Park Hyun-Soo ) - Chungnam National University College of Pharmacy Department of Pharmacology
이도형 ( Lee Do-Hyung ) - Chungnam National University College of Pharmacy Department of Pharmacology
 ( Han Joo-Hui ) - Chungnam National University College of Pharmacy Department of Pharmacology
정상혁 ( Jung Sang-Hyuk ) - Chungnam National University College of Pharmacy Department of Pharmacology
이미지 ( Lee Mi-Ji ) - Chungnam National University College of Pharmacy Department of Pharmacology
장근우 ( Jang Keun-Woo ) - Chungnam National University College of Pharmacy Department of Pharmacology
명창선 ( Myung Chang-Seon ) - Chungnam National University College of Pharmacy Department of Pharmacology

Abstract


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.

키워드

Losartan; Ramipril; Combination therapy; Hypertension; Vascular remodeling

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