Background. In animal models, HMG-CoA reductase inhibitors were able to improve renal function and endothelium-dependent vascular reactivity. In various experimental renal diseases, including autosomal dominant polycystic kidney disease (ADPKD), HMG-CoA reductase inhibitors improved the rate of decline in renal function. We studied the effect of simvastatin on ADPKD patients. Methods. In a double-blind cross-over study, 10 normocholesterolaemic ADPKD patients were treated in random order for 4 weeks with 40 mg simvastatin or placebo daily. After each treatment period, we investigated the effect of simvastatin on renal blood flow and endothelium-dependent vascular reactivity. These periods were separated by a 4-week wash-out period. Results. After treatment with simvastatin, glomerular filtration rate (GFR) significantly increased from 124"4 mlumin to 132"6 mlumin (P-0.05). Simultaneously, effective renal plasma flow (ERPF) increased significantly from 494"30 mlumin to 619"67 mlumin after simvastatin treatment (P-0.05). These renal effects were accompanied by a significantly enhanced vasodilator response to acetylcholine in the forearm after simvastatin treatment. Total serum cholesterol levels were significantly reduced after treatment with simvastatin, from 4.24"0.32 to 3.17"0.22 mmolul (P-0.001). Conclusion. We concluded that simvastatin treatment can ameliorate renal function in ADPKD patients, by increasing renal plasma flow, possibly via improvement of endothelial function. Long-term clinical trials with HMG-CoA reductase inhibitors are needed to confirm these results and to establish a chronic inhibiting effect of HMG-CoA reductase inhibitors on the progression towards end-stage renal disease in ADPKD patients.

Insulin has vasodilating properties in skeletal muscle vasculature that is mediated by increases in nitric oxide, that subsequently stimulates prostaglandin release. The latter appears to be a novel vascular action of insulin.

Objective: To evaluate whether acute elevations of local plasma glucose concentrations could influence forearm blood flow (FBF) and how this interacts with local hyperinsulinaemia in healthy volunteers. Methods: Using the perfused forearm technique, in random order, glucose 20% or saline 0.9% as a control was infused in three dose steps (0.3, 1.0, and 3.0 ml/min) for 5 min each in eight healthy men. The infusion experiments were repeated, in random order, during local hyperinsulinaemia by intra-arterial infusion of insulin 0.05 mU/kg/min. The ratio of FBF of the infused over the FBF in the control arm (FR) was measured at 15-sec intervals during the infusions. Results: Glucose infusion increased the FR dosedependently by 172% ± 39% (M ± SE) at the highest dose (P Ͻ 0.01). During hyperinsulinaemia the glucoseinduced increase in FR was significantly (P Ͻ 0.01) less, 96% ± 26%, however, when changes in FR or forearm

No abstract

No abstract