Many reports have suggested a link between hypertension and insulin resistance and altered glucose homeostasis, but few have determined whether hypertensive arteries have altered transport and metabolism of glucose, and whether such alterations could contribute to the pathogenesis of vascular abnormalities in hypertension. We have recently determined that vascular smooth muscle cells in arteries from several animal models of hypertension have alterations in the expression of the facilitative glucose transporters. For example, aortae and carotid arteries from animals with established DOCA-salt hypertension, a model without classical insulin resistance, show marked reductions in polypeptide levels of GLUT4, the insulin-responsive transporter, with concomitant decreases in glucose uptake and metabolism. Moreover, we have found that altered glucose transporter expression can lead to changes in intracellular Cat+, stress activated protein kinase signaling, and apoptotic pathways in VSMCs, all of which could contribute to vascular abnormalities in hypertension. We also have found that treatment with the thiazolidinedione, troglitazone, can substantially mitigate the hypertensive response in these animals and is accompanied by an increase in GLUT4 levels as well as glucose uptake in arterial VSMCs. Therefore, our hypothesis is that alterations in vascular smooth muscle glucose transporter expression occur during the development of hypertension and contribute directly to functional and structural arterial abnormalities characteristic of hypertension In order to test this hypothesis, we will pursue the following aims: 1. Determine the relative sarcolemmal expression of glucose transporters in VSMCs from DOCA-salt hypertensive and Sham rats. 2. Determine the effects of altered glucose transporter expression on blood pressure, vascular contractility and vascular morphology in DOCA-salt and Sham murine models. To test our hypothesis we will focus on the model of hypertension in which the most profound changes in vascular GLUT4 expression have been found, DOCA-salt hypertension. We will use this model to determine to what extent contractility and vascular morphologic changes of hypertension are due to altered VSMC glucose transporter expression, and in the process reveal basic properties of glucose transporter trafficking in vascular smooth muscle cells. A major tool in this effort will be the study of animal models of altered GLUT4 expression, including GLLTT4 (-/-) and (+/-) knockout mice, and GLUT4 overexpressers. We will also assess the response of these models to DOCA-salt hypertension and treatment with troglitazone. The studies will potentially open up a new understanding of the vascular abnormalities present in hypertension.