Details

Autor(en) / Beteiligte

• Sato, Hidetoshi
• Yaoita, Hiroyuki
• Maehara, Kazuhira
• Maruyama, Yukio

Titel

Attenuation of heart failure due to coronary stenosis by ACE inhibitor and angiotensin receptor blocker

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2003-07, Vol.285 (1), p.H359-H368

Ort / Verlag

United States

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• First Department of Internal Medicine, Fukushima Medical University, Fukushima 960-1295, Japan Submitted 17 July 2002 ; accepted in final form 12 March 2003 It is not known how the angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) attenuate heart failure (HF) in viable ischemic hearts. To assess HF in a rat coronary stenosis (CS) model, we administered vehicle and quinapril or candesartan (or both) orally for 12 wk. Compared with the sham group, the vehicle group showed impaired myocardial perfusion, impaired coronary endothelial nitric oxide (NO) function in vitro, exhausted myocardial mitochondrial respiration, larger left ventricular (LV) dimensions and lower ejection fraction, lower LV rate of pressure development over time (dP/d t ), lower slopes of LV end-systolic pressure-dimension relations (ESPDRs), and increased myocardial fibrosis. Treatment with quinapril or candesartan ameliorated these parameters without modifying the epicardial CS severity. Moreover, their combination maintained similar myocardial perfusion, despite a trend toward lower blood pressure, and showed distinctive neurohumoral modulation, normalized mitochondrial respiration, and increased ESPDR slopes. Thus improved myocardial blood flow and coronary flow reserve by quinapril or candesartan are the key to alleviate CS-induced HF, and their combination may have a therapeutic significance partly through ameliorated mitochondrial respiration and improved LV systolic function. ischemia; rats; nitric oxide; angiotensin-converting enzyme Address for reprint requests and other correspondence: Y. Maruyama, First Dept. of Internal Medicine, Fukushima Medical Univ., Hikarigaoka 1, Fukushima 960-1295, Japan (E-mail: maruyama{at}fmu.ac.jp ).