title: Reduction of heart rate by chronic beta1-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart.
abstract: Adequate growth of coronary vasculature in the remaining left ventricular (LV) myocardium after myocardial infarction (post-MI) is a crucial factor for myocyte survival and performance. We previously demonstrated that post-MI coronary angiogenesis can be stimulated by bradycardia induced with the ATP-sensitive K(+) channel antagonist alinidine. In this study, we tested the hypothesis that heart rate reduction with beta-blockade may also induce coronary growth in the post-MI heart. Transmural MI was induced in 12-mo-old male Sprague-Dawley rats by occlusion of the left anterior descending coronary artery. Bradycardia was induced by administration of the beta-adrenoceptor blocker atenolol (AT) via drinking water (30 mg/day). Three groups of rats were compared: 1) control/sham (C/SH), 2) MI, and 3) MI + AT. In the MI + AT rats, heart rate was consistently reduced by 25-28% compared with C/SH rats. At 4 wk after left anterior descending coronary ligation, infarct size was similar in MI and MI + AT rats (67.1 and 61.5%, respectively), whereas a greater ventricular hypertrophy occurred in bradycardic rats, as indicated by a higher ventricular weight-to-body weight ratio (3.4 +/- 0.1 vs. 2.8 +/- 0.1 mg/g in MI rats). Analysis of LV function revealed a smaller drop in ejection fraction in the MI + AT than in the MI group ( approximately 24 vs. approximately 35%). Furthermore, in MI + AT rats, maximal coronary conductance and coronary perfusion reserve were significantly improved compared with the MI group. The better myocardial perfusion indexes in MI + AT rats were associated with a greater increase in arteriolar length density than in the MI group. Thus chronic reduction of heart rate induced with beta-selective blockade promotes growth of coronary arterioles and, thereby, facilitates regional myocardial perfusion in post-MI hearts.
authors.affiliation: Dept. of Anatomy and Cell Biology, Carver College of Medicine, 1-402 Bowen Science Bldg., Univ. of Iowa, Iowa City, IA 52242, USA. eduard-dedkov@uiowa.edu
authors.forename: Eduard I
authors.initials: EI
authors.lastname: Dedkov
authors.forename: Lance P
authors.initials: LP
authors.lastname: Christensen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Weiss
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tomanek
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology*; D001262:Atenolol / Q000494:pharmacology*; D002302:Cardiac Output; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology / Q000503:physiopathology; D003971:Diastole; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013318:Stroke Volume
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; C022192:alinidine; D003000:Clonidine