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.