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学科主题: 临床医学
题名:
Hypertension induced by nitric oxide synthase inhibitor increases responsiveness of ventricular myocardium and aorta of rat tissue to adrenomedullin stimulation in vitro
作者: Pan, CS; Jiang, W; Zhong, GZ; Zhao, J; Pang, YZ; Tang, CS; Qi, YF
关键词: hypertensive rat ; adrenomedullin ; calcitonin receptor-like receptor ; receptor activity-modifying proteins ; cAMP
刊名: LIFE SCIENCES
发表日期: 2005-12-12
DOI: 10.1016/j.lfs.2005.04.082
卷: 78, 期:4, 页:398-405
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]: Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]: CONGESTIVE-HEART-FAILURE ; GENE-EXPRESSION ; CARDIOVASCULAR-SYSTEM ; RECEPTOR SYSTEM ; PEPTIDE ; ACTIVATION ; SECRETION ; NICOTINE ; NEURONS ; CELLS
英文摘要:

In this work, we aimed to observe the changes in adrenomedullin (ADM) and its receptor-calcitonin receptor-like receptor (CL), receptor activity-modifying protein (RAMP)1, RAMP2 and RAMP3 - in cardiac ventricles and aortas of hypertensive rats, and the responsiveness of injured cardiovascular tissue to ADM, then to illustrate the protective mechanism of ADM on the cardiovascular system. Male SD rats were subjected to treatment with chronic N(G)-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase. The ADM contents and cAMP production in myocardia and aortas were measured by RIA. The mRNA levels of ADM, CL, and RAMP I - 3 were determined by RT-PCR. LNNA induced severe hypertension and cardiomegaly. The ir-ADM content in plasma, ventricles and aortas in L-NNA-treated animals increased by 80%,72% and 57% (all p < 0.01), respectively. Furthermore, mRNA levels of ADM, CL, RAMP2 and RAMP3 were elevated by 91%,33%,50% and 72.5% (all p < 0.01), respectively, in ventricles and by 95%, 177%, 74.7% and 85% (all p < 0.01), respectively, in aortas. mRNA level of RAMPI was elevated by 129% (p < 0.01) in aortas but no significant difference in ventricles. The elevated mRNA levels of RAMP2 and RAMP3 were positively correlated with that of ADM in hypertrophic ventricles (r = 0.633 and 0.828,p < 0.01, respectively) and the elevated mRNA levels of CL, RAMP2 and R-AMP3 were positively correlated with that of ADM in aortas (r = 0.941, 0.943 and 0.736, all p < 0.01, respectively). The response of ventricular myocardia and aortas to ADM administration potentiated, and the production of cAMP was increased by 41% and 68% (both p < 0.01), respectively. ADM-stimulated cAMP generation in ventricular myocardia and aortas was blocked by administration of both ADM(22-52), the specific antagonist of ADM receptor, and CGRP(8-37), the antagonist of the CGRP1 receptor. The results showed an increased in cardiovascular ADM generation and an up-regulation of the gene expression of ADM and its receptor-CL, RAMP1-3 during hypertension, augmented responsiveness of ventricular myocardia and aortas of hypertensive rats to ADM, suggesting that these receptors may play a role in the cardiovascular adaptation in response to sub-chronic NO-inhibition. (c) 2005 Elsevier Inc. All rights reserved.

语种: 英语
WOS记录号: WOS:000233368900010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62319
Appears in Collections:北京大学第一临床医学院_心血管内科_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100083, Peoples R China
2.Peking Univ, Hosp 1, Inst Cardiovasc Dis, Beijing 100034, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100083, Peoples R China

Recommended Citation:
Pan, CS,Jiang, W,Zhong, GZ,et al. Hypertension induced by nitric oxide synthase inhibitor increases responsiveness of ventricular myocardium and aorta of rat tissue to adrenomedullin stimulation in vitro[J]. LIFE SCIENCES,2005,78(4):398-405.
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