The effects of combined treatment of losartan and ramipril on hypertension and related complications
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Journal of Pharmaceutical Investigation https://doi.org/10.1007/s40005-020-00478-9
ORIGINAL ARTICLE
The effects of combined treatment of losartan and ramipril on hypertension and related complications Hyun‑Soo Park1 · Do‑Hyung Lee1 · Joo‑Hui Han1 · Sang‑Hyuk Jung1 · Miji Lee1 · Keun‑Woo Jang1 · Chang‑Seon Myung1 Received: 28 January 2020 / Accepted: 28 March 2020 © The Korean Society of Pharmaceutical Sciences and Technology 2020
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. Keywords Losartan · Ramipril · Combination therapy · Hypertension · Vascular remodeling
Introduction For hypertensive patients with over 140/90 mmHg (systolic/ diastolic blood pressure), a variety of drugs was used for the management of high blood pressure (BP) (Wermelt et al. 2017). Anti-hypertensive drugs are categorized by their mechanisms including angiotensin-converting enzyme inhibitors (ACEIs) (Chen et al. 2018), angiotensin receptor blockers (ARBs) (Hill and Vaidya 2019), β-blockers (Mann 2017), calcium channel blockers (CCBs) (Lin and Ma 2018), diuretics (Roush et al. 2016) and vasodilators (McComb * Chang‑Seon Myung [email protected] 1
Department of Pharmacology, Chungnam National University College of Pharmacy, 99 Daehak‑ro (St.), Yuseong‑gu, Daejeon 34134, Korea
et al. 2016). These drugs can be selected according to the patient’s concomitant disease states including diabetes, heart failure an
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