Effects of Rosiglitazone on Blood Vessels in Patients With High Blood Pressure and High Cholesterol

Cells in the lining of blood vessels produce various substances that cause the vessels to dilate (relax) and constrict (tighten), thereby regulating blood flow. In patients with high blood pressure and high cholesterol, the blood vessels do not dilate properly. This study will investigate the effects of rosiglitazone-a drug used to improve the action of insulin in diabetic patients-on blood flow by examining its effects on endothelin (a substance that causes vessel constriction), and other substances produced by the vessel-lining cells. Adults with blood pressure recordings of 140/90 mmHg or higher on at least three separate days or with a blood cholesterol level of at least 240 mg/dl may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood pressure recordings, blood and urine tests. This "crossover" study involves two separate treatment periods; that is, participants will take either rosiglitazone or placebo (an inactive look-alike pill) once a day for 8 weeks, then no drug for 4 weeks, and then the alternative treatment for the next 8 weeks. Patients will continue to take their high blood pressure medicines during the first 6 weeks of each treatment period. They will stop the medication 2 weeks before the following procedures, which are done at the end of each 8-week treatment period: Strain gauge plethysmography-A small catheter is placed through a needle into an artery at the bend of the arm for measuring blood pressure and drawing blood samples during the study. Pressure cuffs are placed on the wrist and upper arm, and a strain gauge (a rubber band device) is placed around the forearm to measure forearm blood flow. When the cuffs are inflated, blood flows into the arm, stretching the strain gauge at a rate proportional to the flow, and the measurement is recorded. Small doses of four drugs-acetylcholine, bradykinin, sodium nitroprusside and BQ-123-are given through the catheter. Acetylcholine slows t