| Co-Investigator(Kenkyū-buntansha) |
MAEHARA Kazuhira Fukushima Medical University, First Department of Internal Medicine, Associate P, 医学部, 助教授 (90181817)
MARUYAMA Yukio Fukushima Medical University, First Department of Internal Medicine, Professor, 医学部, 教授 (90004712)
|
|---|
| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Research Abstract |
We assessed effects of quinapril, an ACE inhibitor, and candesartan, an AT1-R antagonist, on the development of remodeling of LV induced by fixed coronary stenosis in rats. Stenosis was made by ties at the just proximal site of the left coronary artery. After that, an inert vehicle (vehicle-group), quinapril 10 mg/kg/day (quinapril-group), or candesartan 10 mg/kg/day (candesartan-group) was adiministered orally for 12 weeks. Remodeling was assessed by serial echocardiography, and pathophysiological changes in LV at 12 weeks, by cardiaccatheterization and end-systolic pressure-volume relationships (E.SPVRs), and by measurement of O_2 consumption in myocardial specimens. Myocardial blood flow (MBF) and coronary flow reserve (CFR) were assessed by the colored microsphere method with/without dipyridamole infusion. Results. In the risk area of the vehicle-group, basal MBF and CFR were lower (<.01, both) than those of the age-matched sham-group. The vehicle-group had higher LV weight, lower*
… More
LVdP/dt, higher plasma catecholamines, and higher myocardial O_2 consumption of excised ischemic myocardium with blunted response to bradykinin compared with the sham-group (<.01, each). The vehicle-group developed remodeling indicated by higher end-diastolic (EDV) and end-systolic (ESV) volumes, lower ejection fraction (EP) (<.05, each), and lower (<.01) slopes of ESPVRs than the sham-group. Basal MBF and CER of the quinapril - and candesartan-groups were greater (<.05) than the vehicle-group. These 2 groups attenuated increase in LV weight, plasma catecholamines, LVEDV and LVESV and improved LVEF compared with the vehicle-group. These groups attenuated exhausted in vitro O_2 consumption and improved blunted response of it to bradykinin. Conclusions. Quinapril and candesartan attenuated remodeling of LV exposed to myocardial ischemia attributed to coronary stenosis, Attenuation of coronary endothelial dysfunction and increase in basal MBF appear to be at least in part involved in attenuation of remodeling. The results suggest that ACE inhibition and AT1-R blockade may effectively attenuate remodeling of ischemic LV attributed to coronary stenosis. Less
|
