Acute vasoconstriction-induced insulin resistance in rat muscle in vivo

Insulin-mediated changes in blood flow are associated with altered blood fl ow distribution and increased capillary recruitment in skeletal muscle. Stu dies in perfused rat hindlimb have shown that muscle metabolism can be regu lated by vasoactive agents that control blood flow distribution within the hindlimb, In the present study the effects of a vasoconstrictive agent that has no direct effect on skeletal muscle metabolism but that alters perfusi on distribution in rat hindlimb was investigated in vivo to determine its e ffects on insulin-mediated vascular action and glucose uptake. We measured the effects of alpha-methylserotonin (alpha-met5HT) on mean arterial blood pressure, heart rate, femoral blood flow, hindlimb vascular resistance, and glucose uptake in control and euglycemic insulin-clamped (10 mU.min(-1).kg (-1)) anesthetized rats. Blood flow distribution within the hindlimb muscle s was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an e xogenously added substrate for capillary xanthine oxidase, alpha-Met5HT (20 mu g.min(-1).kg(-1)) infusion alone increased mean arterial blood pressure by 25% and increased hindlimb vascular resistance but caused no change in femoral blood flow. These changes were associated with decreased hindlimb 1 -MX metabolism indicating less capillary flow. Insulin infusion caused decr eased hindlimb vascular resistance that was associated with increased femor al blood flow and 1-MX metabolism. Treatment with alpha-met5HT infusion com menced before insulin infusion prevented the increase in femoral blood flow and inhibited the stimulation of 1-MX metabolism. alpha-Met5HT infusion ha d no effect on hindlimb glucose uptake but markedly inhibited the insulin s timulation of glucose uptake (P < 0.05) and was associated with decreased g lucose infusion rates to maintain euglycemia (P < 0.05), A significant corr elation (P < 0.05) was observed between 1-MX metabolism and hindlimb glucos e uptake but not between femoral blood flow and glucose uptake. The results indicate that in vivo, certain types of vasoconstriction in muscle such as elicited by 5HT(2) agonists, which prevent normal insulin recruitment of c apillary flow, cause impaired muscle glucose uptake. Moreover, if vasoconst riction of this kind results from stress-induced increase in sympathetic ou tflow, then this may provide a clue as to the Link between hypertension and insulin resistance that is often observed in humans.