Feeding rats with high fat diet (HFD) leads to the various conditions of syndrome-X. These are associated with hypertension through a variety of mechanisms. Vascular abnormalities probably contribute to the etiology of many diabetic complications. There is an increase in maximal responses to various agonists with blood vessels of streptozotocin induced diabetic animals. The purpose of this study was to evaluate the development in HFD fed rats for altered biochemical parameters, to assess the vascular responses to phenylephrine (PE), to estimate the KA values and to observe the receptor occupancy. Body weights, plasma triglycerides, cholesterol, and glucose levels were measured every week in male Sprague-Dawley rats. Glucose tolerance test was performed after 4 weeks of feeding. At the end of the fourth week of feeding, concentration-response curves of PE were recorded. Altered KA values of PE (NPD fed rats 2.0 +/- 0.4 microM and HFD fed rats 0.3 +/- 0.1 microM) and receptor occupancy response (NPD fed rats 92.1 +/- 1.7% and HFD fed rats 77.5 +/- 5.6%) strongly suggest that hypertension in HFD fed rats is associated with altered alpha-adrenoceptor function.