van Krimpen C, Smits J F, Cleutjens J P, Debets J J, Schoemaker R G, Struyker Boudier H A, Bosman F T, Daemen M J
Department of Pathology, University of Limburg, Maastricht, The Netherlands.
J Mol Cell Cardiol. 1991 Nov;23(11):1245-53. doi: 10.1016/0022-2828(91)90082-w.
Effects of Captopril. Journal of Molecular and Cellular Cardiology (1991) 23, 1245-1253. This study was undertaken to investigate the alterations in interstitial DNA synthesis and collagen content in the non-infarcted left and right ventricle after induction of a myocardial infarction (MI) in the rat. MI was induced by ligation of the left anterior descending coronary artery. All animals received 5-Bromo-2'-deoxyUridine (BrdU), via a subcutaneous osmotic minipump, one day before sacrifice, to quantitate DNA synthesis. A transient rise in BrdU incorporation was found in both ventricles. Peak levels were found at day 7 and 14 after infarct induction. BrdU incorporation had returned to control levels 3 weeks after infarct induction. By using anti BRDU--anti-laminin immuno- double staining DNA synthesis was localized mainly in the cardiac interstitium. Concomitantly, a sustained increase in collagen content, measured as the Sirius red positive area on cross sections, was found from day 7 after infarct induction. No changes were found in sham animals. In the second part of the study the effects of the angiotensin I converting enzyme inhibitor captopril and the arteriolar vasodilator hydralazine on MI induced interstitial DNA synthesis and collagen content were investigated. Captopril reduced both the increase in DNA synthesis and collagen content. Hydralazine did not affect interstitial DNA synthesis, but reduced the MI induced collagen content. Both drugs had no effects in sham animals. We conclude that induction of a myocardial infarction stimulates interstitial DNA synthesis and increases the collagen content in the non-infarcted areas of the heart. Interstitial DNA synthesis is dependent on the angiotensin I converting enzyme in a direct manner independent from afterload changes.
卡托普利的作用。《分子与细胞心脏病学杂志》（1991年）23卷，1245 - 1253页。本研究旨在探究大鼠心肌梗死（MI）诱导后，非梗死左、右心室间质DNA合成及胶原蛋白含量的变化。通过结扎左冠状动脉前降支诱导MI。所有动物在处死前一天，经皮下渗透微型泵给予5 - 溴 - 2'-脱氧尿苷（BrdU），以定量DNA合成。在两个心室均发现BrdU掺入量短暂升高。梗死诱导后第7天和第14天达到峰值水平。梗死诱导3周后，BrdU掺入量恢复至对照水平。通过抗BrdU - 抗层粘连蛋白免疫双染色，发现DNA合成主要定位于心脏间质。同时，从梗死诱导后第7天开始，以天狼星红阳性面积衡量的胶原蛋白含量持续增加。假手术动物未发现变化。在研究的第二部分，研究了血管紧张素I转换酶抑制剂卡托普利和小动脉血管扩张剂肼屈嗪对MI诱导的间质DNA合成及胶原蛋白含量的影响。卡托普利降低了DNA合成及胶原蛋白含量的增加。肼屈嗪不影响间质DNA合成，但降低了MI诱导的胶原蛋白含量。两种药物对假手术动物均无作用。我们得出结论，心肌梗死的诱导刺激了间质DNA合成，并增加了心脏非梗死区域的胶原蛋白含量。间质DNA合成直接依赖于血管紧张素I转换酶，独立于后负荷变化。
