Effect of metformin on the vascular and glucose metabolic actions of insulin in hypertensive rats

We investigated the long-term effect of metformin treatment on blood pressu re, insulin sensitivity, and vascular responses to insulin in conscious spo ntaneously hypertensive rats (SHR). The rats were instrumented with intrava scular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and blood flow. Insulin sensitivity was assessed by the euglyce mic hyperinsulinemic clamp technique. Two groups of SHR received metformin (100 or 300 mg . kg(-1) . day(-1)) for 3 wk while another group of SHR and a group of Wistar Kyoto (WKY) rats were left untreated. We found that vasod ilation of skeletal muscle and renal vasculatures by insulin is impaired in SHR. Moreover, a reduced insulin sensitivity was detected in vivo and in v itro in isolated soleus and extensor digitorum longus muscles from SHR comp ared with WKY rats. Three weeks of treatment with metformin improves the wh ole-body insulin-mediated glucose disposal in SHR hut has no blood pressure -lowering effect and no influence on vascular responses to insulin (4 mU . kg(-1) . min(-1)). An improvement in insulin-mediated glucose transport act ivity was detected in isolated muscles from metformin-treated SHR, but in t he absence of insulin no changes in basal glucose transport activity were o bserved. It is suggested that part of the beneficial effect of metformin on insulin resistance results from a potentiation of the hormone-stimulating effect on glucose transport in peripheral tissues (mainly skeletal muscle). The results argue against a significant antihypertensive or vascular effec t of metformin in SHR.