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纳米载药阿利克仑对自发性高血压大鼠心血管系统的保护作用。

Protective Effects of Nanoparticle-Loaded Aliskiren on Cardiovascular System in Spontaneously Hypertensive Rats.

机构信息

Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovakia.

Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Kosice, Slovakia.

出版信息

Molecules. 2019 Jul 25;24(15):2710. doi: 10.3390/molecules24152710.

Abstract

Aliskiren, a renin inhibitor, has been shown to have cardioprotective and blood pressure (BP) lowering effects. We aimed to determine the effects of nanoparticle-loaded aliskiren on BP, nitric oxide synthase activity (NOS) and structural alterations of the heart and aorta developed due to spontaneous hypertension in rats. Twelve week-old male spontaneously hypertensive rats (SHR) were divided into the untreated group, group treated with powdered or nanoparticle-loaded aliskiren (25 mg/kg/day) and group treated with nanoparticles only for 3 weeks by gavage. BP was measured by tail-cuff plethysmography. NOS activity, eNOS and nNOS protein expressions, and collagen content were determined in both the heart and aorta. Vasoactivity of the mesenteric artery and wall thickness, inner diameter, and cross-sectional area (CSA) of the aorta were analyzed. After 3 weeks, BP was lower in both powdered and nanoparticle-loaded aliskiren groups with a more pronounced effect in the latter case. Only nanoparticle-loaded aliskiren increased the expression of nNOS along with increased NOS activity in the heart (by 30%). Moreover, nanoparticle-loaded aliskiren decreased vasoconstriction of the mesenteric artery and collagen content (by 11%), and CSA (by 25%) in the aorta compared to the powdered aliskiren group. In conclusion, nanoparticle-loaded aliskiren represents a promising drug with antihypertensive and cardioprotective effects.

摘要

阿利克仑是一种肾素抑制剂,已被证明具有心脏保护和降低血压(BP)的作用。我们旨在确定载纳米粒子的阿利克仑对自发性高血压大鼠因自发性高血压引起的血压、一氧化氮合酶活性(NOS)和心脏及主动脉结构改变的影响。12 周龄雄性自发性高血压大鼠(SHR)通过灌胃分为未治疗组、粉末或载纳米粒子的阿利克仑(25mg/kg/天)治疗组和仅载纳米粒子治疗组(3 周)。通过尾套测压法测量血压。测定心脏和主动脉中的 NOS 活性、eNOS 和 nNOS 蛋白表达以及胶原含量。分析肠系膜动脉的血管活性、壁厚度、内直径和主动脉横截面积(CSA)。3 周后,粉末和载纳米粒子阿利克仑组的血压均降低,后者的降压作用更为明显。只有载纳米粒子的阿利克仑增加了心脏中 nNOS 的表达,并增加了 NOS 活性(增加 30%)。此外,与粉末阿利克仑组相比,载纳米粒子的阿利克仑降低了肠系膜动脉的血管收缩和胶原含量(减少 11%)以及主动脉 CSA(减少 25%)。总之,载纳米粒子的阿利克仑是一种具有降压和心脏保护作用的有前途的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2773/6695910/f441ca227e3c/molecules-24-02710-g001.jpg

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