Development of intravital microscope for measurement of capillary and coronary blood flow, and coronary microvascular disturbance of diabetes mellitus and circulatory reconstruction

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It was possible to visualize the blood capillary and observe the coronary microcirculation in dogs of diabetes mellitus by a CCD intravital microscope of high accuracy. We have demonstrated that endothelium-derived hyperpolarizing factors (EDHF)/H_2O_2 and NO were key mediators of vasodilatation of coronary native collateral microvassels after myocardial ischemia, and erythropoietin (EPO) and angiotensin receptor blockers (ARB) enhanced the vasodilatation in canine coronary collateral microvessels in vivo, and also enhanced H_2O_2-induced canine coronary collateral vasodilatation. Myocardial expression of eNOS and Akt activity as the ratio of phospho-Akt/total Akt in the myocardium of ischemic LAD area of control group were increased by EPO. These results indicate that EPO improves eNOS protein expression and Akt phosphorylation, at least in part, through activation of PI3K/Akt and EDHF/H_2O_2 pathway. EPO, ARB and EDHF/H_2O_2 play an important role for improvement factor of vascular endothelial disturbance.