Castoldi G, di Gioia C R, Pieruzzi F, van De Greef W M, Busca G, Sperti G, Stella A
U.D.A. Nefrocardiovascolare, Dipartimento di Medicina Clinica, Prevenzione e Biotecnologie Sanitarie, Università degli Studi di Milano-Bicocca, Monza, Italy.
J Hypertens. 2001 Nov;19(11):2011-8. doi: 10.1097/00004872-200111000-00011.
It has been shown that angiotensin II (Ang II) induces the expression of calponin, a 34 kD actin-binding protein, in vascular smooth muscle cells in vitro. The aim of this study was to investigate whether Ang II can modulate calponin gene expression in rat aorta in vivo.
Aortic calponin gene expression was studied after chronic exogenous Ang II administration and in Goldblatt hypertension.
To investigate the effect of Ang II administration, Sprague Dawley rats were treated for 6 days with a continuous infusion of Ang II (200 ng/kg per min) or saline by osmotic minipumps. The effect of endogenous Ang II on aortic calponin mRNA expression was studied in Goldblatt hypertensive rats with (2K1C model), or without (1K1C model) activation of the renin-angiotensin system. In particular, calponin gene expression in 2K1C rats was studied both at 1 week (2K1C-HR, high renin) and 4 weeks after the onset of hypertension, when plasma renin activity (PRA) was returned to normal values (2K1C-NR, normal renin). Systolic blood pressure (SBP) was measured twice a week. At the end of the experimental period, PRA was measured by radioimmunoassay, and aortic calponin gene expression was measured by Northern hybridization.
SBP was significantly higher (P < 0.01), whereas PRA was suppressed (P < 0.01), in Ang II versus saline-treated rats. Northern hybridization showed that the aortic calponin gene expression significantly increased (2.5-fold) in Ang II-treated rats (P = 0.01). In Goldblatt hypertensive rats, SBP was significantly higher in 2K1C-HR (P < 0.01), 2K1C-NR (P < 0.01) and 1K1C (P < 0.01) rats compared with the corresponding sham-treated rats. Activation of the renin-angiotensin system was present only in 2K1C-HR rats (P < 0.01), and Northern analysis showed that aortic calponin mRNA expression was significantly increased (2.2-fold) in this group of rats only (P < 0.01).
Our data demonstrate that both exogenous and endogenous Ang II increase calponin gene expression in aortic smooth muscle cells, independently of the hemodynamic effect of Ang II.
已有研究表明，血管紧张素II（Ang II）可在体外诱导血管平滑肌细胞中钙调蛋白（一种34 kD的肌动蛋白结合蛋白）的表达。本研究旨在探讨Ang II在体内是否能调节大鼠主动脉中钙调蛋白基因的表达。
在慢性外源性给予Ang II后以及在Goldblatt高血压模型中研究主动脉钙调蛋白基因的表达。
为研究给予Ang II的作用，通过渗透微型泵连续输注Ang II（200 ng/kg每分钟）或生理盐水，对Sprague Dawley大鼠进行6天的治疗。在激活肾素-血管紧张素系统的（2K1C模型）或未激活该系统的（1K1C模型）Goldblatt高血压大鼠中研究内源性Ang II对主动脉钙调蛋白mRNA表达的影响。特别地，对2K1C大鼠在高血压发作后1周（2K1C-HR，高肾素）和4周时（此时血浆肾素活性（PRA）恢复到正常水平，即2K1C-NR，正常肾素）的钙调蛋白基因表达进行研究。每周测量两次收缩压（SBP）。在实验期结束时，通过放射免疫测定法测量PRA，并通过Northern杂交法测量主动脉钙调蛋白基因的表达。
与生理盐水处理的大鼠相比，Ang II处理的大鼠SBP显著升高（P < 0.01），而PRA受到抑制（P < 0.01）。Northern杂交显示，Ang II处理的大鼠主动脉钙调蛋白基因表达显著增加（2.5倍）（P = 0.01）。在Goldblatt高血压大鼠中，与相应的假手术处理大鼠相比，2K1C-HR（P < 0.01）、2K1C-NR（P < 0.01）和1K1C（P < 0.01）大鼠的SBP显著更高。仅在2K1C-HR大鼠中存在肾素-血管紧张素系统的激活（P < 0.01），Northern分析显示仅在这组大鼠中主动脉钙调蛋白mRNA表达显著增加（2.2倍）（P < 0.01）。
我们的数据表明，外源性和内源性Ang II均可增加主动脉平滑肌细胞中钙调蛋白基因的表达，且与Ang II的血流动力学效应无关。
