DNA synthesis in the non-infarcted cardiac interstitium after left coronary artery ligation in the rat: effects of captopril.

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.