DIFFERENTIAL-EFFECTS OF KININS ON CARDIOMYOCYTE HYPERTROPHY AND INTERSTITIAL COLLAGEN MATRIX IN THE SURVIVING MYOCARDIUM AFTER MYOCARDIAL-INFARCTION IN THE RAT

Background Left ventricular remodeling after myocardial infarction (MI ) involves the hypertrophic growth of cardiomyocytes and the accumulat ion of fibrillar collagen in the interstitial space. We evaluated the role of kinins in postinfarction ventricular remodeling and their pote ntial contribution to the antiremodeling effects of ACE inhibition and angiotensin II type 1 (AT1) receptor blockade. Methods and Results Ra ts underwent coronary artery ligation followed by chronic B2 kinin rec eptor blockade with icatibant. Additional groups of infarcted rats wer e treated with the ACE inhibitor lisinopril or the AT1 receptor antago nist ZD7155, each separately and in combination with icatibant. B2 kin in receptor blockade enhanced the interstitial deposition of collagen after MI, whereas morphological and molecular markers of cardiomyocyte hypertrophy (cardiac weight, myocyte cross-sectional area, prepro-atr ial natriuretic factor mRNA expression) were not affected. Chronic ACE inhibition and AT1 receptor blockade reduced collagen deposition and cardiomyocyte hypertrophy after MI. The inhibitory action of ACE inhib ition and AT1 receptor blockade on interstitial collagen was partially reversed by B2 kinin receptor blockade. However, B2 kinin receptor bl ockade did not attenuate the effects of ACE inhibition and AT1 recepto r blockade on cardiomyocyte hypertrophy. Conclusions (1) Kinins inhibi t the interstitial accumulation of collagen but do not modulate cardio myocyte hyper trophy after MI. (2) Kinins contribute to the reduction of myocardial collagen accumulation by ACE inhibition and AT1 receptor blockade. (3) The effects of ACE inhibition and AT1 receptor blockade on cardiomyocyte hypertrophy are related to a reduced generation/rece ptor blockade of angiotensin II.