EFFECT OF INSULIN ON RENAL SODIUM AND URIC-ACID HANDLING IN ESSENTIAL-HYPERTENSION

In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of in sulin are altered in insulin resistant hypertension. In 37 patients wi th essential hypertension, we measured the changes in urinary excretio n of sodium, potassium, and uric acid in response to physiological eug lycemic hyperinsulinemia (by using the insulin clamp technique at an i nsulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 +/- 1.5 mu mol/min/kg, ie, 20% lower than in normotensive contro ls (33.1 +/- 2.1 mu mol/min/kg, P = .015). In the basal state, fasting plasma uric acid concentrations were higher in men than women (P < .0 01), were positively related to body mass index (r = 0.38, P = .02), w aist/hip ratio (r = 0.35, P < .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentra tions (r = -0.59, P = .0001) and glucose disposal rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P < .0001) and triglyceride concentrations (r = 0.39, P < .02), and direct ly related to HDL cholesterol levels (r = 0.52, P < .001). During insu lin infusion, blood pressure, plasma uric acid and sodium concentratio n, and creatinine clearance did not change. In contrast, hyperinsuline mia caused a significant decrease in the urinary excretion of uric aci d (2.67 +/- 0.12 to 1.86 +/- .14 mu mol/min/1.73 m(2), P = .0001), sod ium (184 +/- 12 to 137 +/- 14 mu mol/l/1.73 m(2), P = .0001), and pota ssium (81 +/- 7 to 48 +/- 4 mu mol/min/1.73 m(2), P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percenta gewise, these changes were similar to those found in normotensive subj ects. Insulin-induced changes in urate excretion were coupled (r = 0.5 5, P < .0001) to the respective changes in sodium excretion. In hypert ensive patients, higher uric acid levels and lower renal urate clearan ce rates cluster with insulin resistance and dyslipidemia. Despite ins ulin resistance of glucose metabolism, acute physiological hyperinsuli nemia causes normal antinatriuresis, antikaliuresis, and antiuricosuri a in these patients.