Vascular Smooth Muscle Hyperactivity and Type II Diabetes--Associated Hypertension

Type II diabetes is one of the most serious long-term health problems in the United States that causes enormous social and economic consequences. Hypertension is common among obese type II diabetic patients and is a major causative factor of cardiovascular events in type II diabetes. However, the pathogenic interactions between diabetes and hypertension remain unclear. We observed severe hypertension and enhanced vascular smooth muscle contractile response in leprdbidb mice, a mice model resembles human type II diabetes. Since tone of vascular smooth muscle is an important determinant of the radius of arterioles and thus blood pressure, we wanted to elucidate the molecular mechanisms underlying the observed vascular smooth muscle hyperreactivity and its role in the diabetes-associated hypertension. To achieve these goals, we propose to test a novel hypothesis that increase in contractile prostanoid production in vascular smooth muscle causes vascular smooth muscle hyperreactivity and therefore contribute to the cause of diabetes-associated hypertension. Results of the proposed study may provide new insight into the pathogenesis of diabetes- associated hypertension and potential new therapeutic target for the prevention and treatment of cardiovascular complication of diabetes.