Effects of an AT(1) receptor antagonist, an ACE inhibitor and a calcium channel antagonist on cardiac gene expressions in hypertensive rats
Effects of an AT(1) receptor antagonist, an ACE inhibitor and a calcium channel antagonist on cardiac gene expressions in hypertensive rats
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DOI：
10.1111/j.1476-5381.1996.tb15437.x
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发表时间：
1996-06-01
影响因子：
7.3
通讯作者：
Iwao, H
中科院分区：
文献类型：
--
作者：
Kim, S;Ohta, K;Iwao, H
1 本研究旨在确定 AT(1) 受体是否直接导致高血压诱发的心脏肥大和基因表达。2 向易发生中风的自发性高血压大鼠 (SHRSP) 口服 AT(1) 受体拮抗剂（氯沙坦，30 mg kg(-1)day(-1)）、一种血管紧张素转换酶抑制剂（依那普利 10 mg） kg(-1) 天(-1))、二氢吡啶类钙通道拮抗剂（氨氯地平，5 mg kg(-1)天(-1)）或媒介物（对照），持续 8 周（16 至 24 周龄）。比较每种药物对心室重量以及心肌表型和纤维化相关基因 mRNA 水平的影响。 3 SHRSP 的左心室肥大伴随着两种胎儿表型收缩蛋白（骨骼 α-肌动蛋白和 β-肌球蛋白重链 (β-MHC)）、心房钠尿肽 (ANP)、 转化生长因子-β-1 (TGF-β 1) 和胶原蛋白，以及成人收缩蛋白 (α-MHC) 表型的 mRNA 水平下降。因此，SHRSP 左心室的特征是心肌从成人表型向胎儿表型的转变以及分子水平上的间质纤维化。 4 虽然氯沙坦、依那普利和氨氯地平在整个治疗过程中将 SHRSP 的血压降低到相当的程度，但氯沙坦比氨氯地平更大程度地使 SHRSP 左心室肥厚消退（P
1 This study was undertaken to determine whether the AT(1) receptor directly contributes to hypertension-induced cardiac hypertrophy and gene expressions.2 Stroke-prone spontaneously hypertensive rats (SHRSP) were given orally an AT(1) receptor antagonist (losartan, 30 mg kg(-1)day(-1)), an angiotensin converting enzyme inhibitor (enalapril 10 mg kg(-1) day(-1)), a dihydropyridine calcium channel antagonist (amlodipine, 5 mg kg(-1)day(-1)), or vehicle (control), for 8 weeks (from 16 to 24 weeks of age). The effects of each drug were compared on ventricular weight and mRNA levels for myocardial phenotype- and fibrosis-related genes.3 Left ventricular hypertrophy of SHRSP was accompanied by the increase in mRNA levels for two foetal phenotypes of contractile proteins (skeletal alpha-actin and beta-myosin heavy chain (beta-MHC)), atrial natriuretic polypeptide (ANP), transforming growth factor-beta-1 (TGF-beta 1) and collagen, and a decrease in mRNA levels for an adult phenotype of contractile protein (alpha-MHC). Thus, the left ventricle of SHRSP was characterized by myocardial transition from an adult to a foetal phenotype and interstitial fibrosis at the molecular level.4 Although losartan, enalapril and amlodipine lowered blood pressure of SHRSP to a comparable degree throughout the treatment, losartan caused regression of left ventricular hypertrophy of SHRSP to a greater extent than amlodipine (P