Febuxostat, Blood Pressure and the Intrarenal Renin-Angiotensin System (RAS)
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In this study the investigators will recruit hypertensive subjects with higher than average uric acid levels to test the effect of lowering uric acid with febuxostat on several measures as listed below. This will be a randomized, double-blind, placebo-controlled, parallel group study.
Change in Renal Plasma Flow in Response to Infused Angiotensin II [ Time Frame: Baseline to 6 weeks ]
Secondary Outcome Measures :
Change in Endothelial Function [ Time Frame: Baseline to 6 weeks ]
Endothelial function was calculated by software from the manufacturer VENDYS. The measurement was taken by using the index of area under the curve of the finger temperature recovery curve just after releasing a blood pressure cuff. The blood pressure cuff occluded blood flow for 5 minutes as compared to the temperature curve in the non-occluded arm.
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Ages Eligible for Study:
18 Years to 60 Years (Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Mild to moderate hypertension. For purposes of this study, the investigators define mild to moderate hypertension as being on no more than 1-2 antihypertensive medications and blood pressure <140 mm Hg systolic and <90 mm Hg diastolic based on mean seated blood pressure at the screening visit in our clinic. For these visits, the investigators measure blood pressure using a Dinamap automatic oscillometric cuff while subjects are seated quietly. The subjects are left in a quiet room without speaking for 5 minutes initially. The Dinamap is started and the technician leaves the room and 3 blood pressures are obtained at intervals of 2 minutes. The investigators use the mean of last 2 blood pressures for classification purposes. This is the approach the investigators have used in several multicenter studies including HyperGEN and the NHLBI Family Heart Study.
Age 18 to 60.
Uric acid =5.8 mg/dl. This was the mean uric acid among hypertensives in our prior study.11 As renal plasma flow response to Ang II infusion decreased linearly with higher uric acid, the investigators felt that using higher than average uric acid will provide greater power.
Severe or poorly controlled hypertension (treated blood pressure >160 mm Hg systolic or >100 mm Hg diastolic).
Diabetes (type 1 or type 2).
Estimated GFR <60 ml/min.
Persons unable stop all medications (including antihypertensives) other than stable doses of thyroxine or estrogen for at least 2 weeks.
Prior history of clinically diagnosed coronary artery disease or congestive heart failure.
Taking uric acid lowering medication within 1 month of screening visit.