Recently, it has been demonstrated that insulin resistance, as well as endothelial dysfunction, has a very close association with many common diseases, such as diabetes mellitus, dyslipidemia and hypertension with these diseases comes the risk of atherosclerosis, with can lead to fatal cardiovascular disorders such as stroke and ischemic heart disease. We have approached the pathogenesis and underlying mechanisms of prophylaxis and therapeutics of these diseases using animal and cellular models.
In this laboratory, we investigate the effect of certain drugs on myocardial infarction and septicemia, which cause heart failure in rat models and cultured myocardial cell lines, respectively. Langendorf-perfused rat hearts are utilized to examine the protective effect of "pre-conditioning" on ishcemic-reperfusion injury. We have also been attempting to clarify the relationship between endothelial dysfunction and diseases such as hypertension, hyperlipidemia and impaired glucose tolerance, which are included in "insulin resistant syndrome or metabolic syndrome". Thus far, we have analyzed the "pleiotropic effects" directly related to the vascular endothelial protection of therapeutic agents for hyperlipidemia and hyperglycemia. To do this, we use pharmacological, biochemical and molecular biological techniques on dissociated cultured vascular endothelial cells and ring preparations from a rat's aorta and smaller arteries such as the mesenteric, vertebral and renal arteries. We are also interested in the central mechanisms involved in the development of hypertension. Local release of catecholamine and nitric oxide in the hypothalamus and medulla are examined in hypertensive and normotensive rats, using a brain microdialysis technique.