부산대학교 도서관

Patients with diabetes mellitus have a higher risk for cardiovascular disease. Endothelial dysfunction caused by reduced bioavailability of nitric oxide (NO) and oxidative stress has been identified as an early event in diabetic vascular diseases. However, the mechanisms of impaired cardiac microcirculation in diabetes remain incompletely understood. The origins of endothelial cells of aortic and mesenteric arteries are different from that of coronary arteries so the mechanism of vessel dilation in diabetic aortic and mesenteric arteries which are mostly used might be different in the diabetic mouse coronary arteries. Moreover, NO is the major vasodilatory metabolite in the coronary circulation, but the dilation in patients with coronary artery diseases is switched from NO dependent to H2O2 dependent. Our study will address if there is such a switch in the diabetic coronary circulation. Five groups of mice were used: young and old wild type (WT) mice, WT mice on high fat/high sugar (HFHS) diet (diet-induced diabetic model), and young and old db/db mice. Coronary arteries were isolated and incubated in an organ bath perfused with agonist/inhibitor, and vasodilation was recorded with a DMT myograph. NO production in vascular rings were measured. Our preliminary data show: 1) Coronary dilation induced by acetylcholine (Ach) decreased more in old db/db mice than that in young db/db mice. The extent of coronary dilation in diet-induced diabetic mice was in between wild type and db/db mice. 2) In diabetic mice, L-NAME inhibited vasorelaxation of the aorta, but not coronary arteries. 3) Peg-catalase inhibited coronary dilation in diabetic mice. 4) Mito-Tempol improved coronary dilation in young diabetic mice, not old diabetic mice. 5) L-NAME did not change NO production in diabetic mice during dilation as it did in WT. These results suggest that vascular dysfunction in diet-induced diabetic mice is less severe than that in db/db mice. Coronary dilation in diabetic mice is H2O2 dependent, not NO dependent. Mitochondrial dysfunction might be involved in this switch. Further study of the underlying mechanism will lead to the treatment to ameliorate the dysfunction of cardiac microcirculation in diabetes.