LOSARTAN MEDIATED IMPROVEMENT IN INSULIN ACTION IS MAINLY DUE TO AN INCREASE IN NONOXIDATIVE GLUCOSE-METABOLISM AND BLOOD-FLOW IN INSULIN-RESISTANT HYPERTENSIVE PATIENTS

We investigated the possible role of losartan on insulin-mediated gluc ose uptake, substrate oxidation and blood flow in insulin-resistant hy pertensive patients. Sixteen newly diagnosed patients with mild-to-mod erate hypertension were studied. The study design was a single-blind, randomised, placebo-controlled trial. After a 1 week run-in period, ea ch patient was randomly assigned to placebo (n=7) and losartan (n=9). Both treatment periods lasted 4 weeks, At baseline, and at the end of the placebo and losartan treatment periods, euglycaemic hyperinsulinae mic glucose clamp and indirect calorimetry were performed. Before and along each glucose clamp, blood Row was also determined in the femoral artery by image-directed duplex ultrasonography combining B-mode imag ing and pulse Doppler beams. Losartan vs placebo lowered systolic bloo d pressure by 163 +/- 3.5 and 147 +/- 4.1 mm Hg (P < 0.001), and diast olic blood pressure by 95 +/- 3.2 and 85 +/- 3.2 mmHg (P < 0.001). Los artan enhanced glucose metabolic clearance rate by 5.1 +/- 0.3 and 6.3 +/- 0.4 mg/kg x min (P < 0.05), and whole body glucose disposal (WBGD ) by 29.2 +/- 0.5 and 38.1 +/- 0.4 mu mol/kg free fatty mass (FFM) x m in (P < 0.01) but did not affect heart rate. Insulin-mediated change i n blood flow was greater after losartan than placebo administration (1 11 +/- 4 vs 84 +/- 3%, P < 0.01). Per cent change in insulin-mediated stimulation of blood flow and WBGD were also correlated (r=0.76, P<0.0 1). Analysis of substrate oxidation revealed that losartan adminstrati on improved insulin action and non-oxidative glucose metabolism (NOGM) (30.8 +/- 2.2 vs 22.8 +/- 2.8 mu mol/kg FFM x min, P < 0.05), In conc lusion losartan improves insulin-mediated glucose uptake through an in crease in NOGM and blood flow in hypertensive patients.