Bell David, Kelso Elizabeth J, Argent Cymone C H, Lee Graham R, Allen Adrian R, McDermott Barbara J
Department of Therapeutics and Pharmacology, Centre for Cardiovascular and Genetics Research, School of Medicine, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
Cardiovasc Pathol. 2004 Mar-Apr;13(2):71-8. doi: 10.1016/S1054-8807(03)00135-2.
The spontaneously hypertensive rat (SHR) is frequently used as model of cardiovascular disease, with considerable disparity in reported parameters of hypertrophy. The aim of this study was to assess the temporal changes occurring during the development and progression of cardiomyocyte hypertrophy in SHR, subsequent to pressure overload, compared to changes associated with normal aging using the normotensive Wistar-Kyoto (WKY) rat.
Ventricular cardiomyocytes were isolated from rats at 8, 12, 16, 20 and 24 weeks, and parameters of hypertrophy (cell dimensions, protein mass, de novo protein synthesis, and gene expression) and function (contraction and hypertrophic responsiveness in vitro) were assessed.
Hypertension was evident at > or =7 weeks in SHRs. Heart:body mass ratio, cardiomyocyte protein mass and width were elevated (P<.05) in SHRs at 16-20 weeks compared to WKYs. In SHRs compared to WKYs at 16 weeks, there was a transient increase (P<.05) in protein synthesis, enhanced hypertrophic responsiveness to phorbol-12-myristate-13-acetate, and induced hypertrophic responsiveness to isoprenaline. Skeletal-alpha-actin mRNA was detected in SHR but not WKY cells at all ages. ANP mRNA was lower in SHR than in WKY cells at 8-20, but progressively increased (P<.05) from 12 to 24 weeks within SHRs. Contractile function increased (P<.05) at 20 weeks in SHR compared to WKY rats.
Structural and functional changes occurring at the cellular level in the myocardium of SHR follow a distinct pattern, such that pressure overload was initially accompanied by expressional changes (8-12 weeks), followed by active hypertrophic growth and enhanced function (16-20 weeks), which subsequently decelerated as stable compensation was attained.
自发性高血压大鼠（SHR）常被用作心血管疾病模型，但其报道的肥大参数存在相当大的差异。本研究的目的是评估压力超负荷后，SHR心肌细胞肥大发生和发展过程中的时间变化，并与正常血压的Wistar-Kyoto（WKY）大鼠正常衰老相关变化进行比较。
在8、12、16、20和24周时从大鼠分离心室心肌细胞，评估肥大参数（细胞大小、蛋白质质量、新生蛋白质合成和基因表达）和功能（体外收缩和肥大反应性）。
SHR在≥7周时出现明显高血压。与WKY相比，SHR在16 - 20周时心脏与体重比、心肌细胞蛋白质质量和宽度升高（P<0.05）。与16周时的WKY相比，SHR的蛋白质合成短暂增加（P<0.05），对佛波醇-12-肉豆蔻酸酯-13-乙酸酯的肥大反应性增强，对异丙肾上腺素的肥大反应性诱导增强。所有年龄段的SHR细胞中均检测到骨骼肌α-肌动蛋白mRNA，而WKY细胞中未检测到。在8 - 20周时，SHR细胞中的心房钠尿肽mRNA低于WKY细胞，但在SHR中从12周到24周逐渐增加（P<0.05）。与WKY大鼠相比，SHR在20周时收缩功能增加（P<0.05）。
SHR心肌细胞水平发生的结构和功能变化遵循独特模式，压力超负荷最初伴有表达变化（8 - 12周），随后是活跃的肥大生长和功能增强（16 - 20周），随着达到稳定代偿，随后变化减缓。
