Attenuation of heart failure due to coronary stenosis by ACE inhibitor and angiotensin receptor blocker.
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/dt), 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.
Sato
Hidetoshi
H
First Department of Internal Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.
Yaoita
Hiroyuki
H
Maehara
Kazuhira
K
Maruyama
Yukio
Y
D000758:Anesthesia; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D006328:Cardiac Catheterization; D003326:Coronary Circulation / Q000502:physiology; D023921:Coronary Stenosis / Q000150:complications*; D004452:Echocardiography; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006339:Heart Rate / Q000502:physiology; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D013318:Stroke Volume / Q000502:physiology; D016019:Survival Analysis; D016277:Ventricular Function, Left / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D018377:Neurotransmitter Agents; D044140:Receptor, Angiotensin, Type 1