The kallikrein-kinin system in post-myocardial infarction cardiac remodeling.
Angiotensin converting-enzyme (ACE) inhibitors attenuate cardiac hypertrophy and prolong survival in animal models and patients after myocardial infarction (MI). Considering the dual function of the ACE, the therapeutic efficacy of ACE inhibitors after MI implicates the renin-angiotensin system and/or the kallikrein-kinin system in the pathophysiology of postinfarction cardiac remodeling. We evaluated the role of kinins, and their potential contribution to the antiremodeling effects of ACE inhibition in this setting. Rats underwent coronary artery ligation followed by chronic B2 kinin receptor blockade with icatibant (HOE 140). Additional groups of MI rats were treated with the ACE inhibitor lisinopril, alone or in combination with icatibant. B2 kinin receptor blockade enhanced the deposition of collagen (morphometric analysis) in the left ventricular interstitial space after MI, whereas markers of cardiomyocyte hypertrophy (left ventricular weights and prepro-atrial natriuretic factor [ANF] expression) were not affected. Chronic ACE inhibition reduced collagen deposition and cardiomyocyte hypertrophy after MI. The inhibitory action of ACE inhibition on interstitial collagen was partially reversed by B2 kinin receptor blockade. However, B2 kinin receptor blockade did not attenuate the effects of ACE inhibition on cardiomyocyte hypertrophy. In conclusion, kinins inhibit the interstitial accumulation of collagen, but do not modulate cardiomyocyte hypertrophy after MI. Kinins contribute to the reduction of myocardial collagen accumulation by ACE inhibition; however, the effects of ACE inhibition on cardiomyocyte hypertrophy are related to reduced generation of angiotensin II.
Wollert
K C
KC
Abteilung Kardiologie, Medizinische Hochschule Hannover, Germany.
Drexler
H
H
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D003250:Constriction; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D016234:Kallikrein-Kinin System; D017706:Lisinopril / Q000494:pharmacology; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D051381:Rats
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; C065679:icatibant; D017706:Lisinopril; D001920:Bradykinin