DIRECT VASODILATORY EFFECT OF INSULIN ON ISOLATED RETINAL ARTERIOLES

Purpose. To test the hypothesis that insulin has a direct vasodilatory effect on retinal arteries and their branches and to investigate the mechanisms involved. Methods. Segments of porcine retinal arteries wer e dissected, cannulated, and perfused. Vessel diameter was measured co ntinuously on-line. Vessels were precontracted to 66%+/-0.9% (SEM, n=1 48) of their original diameter by perfusing with 124 mM K+-Krebs solut ion. Dose-response curves to insulin (2 to 2000 mu U/ml) were compared for extraluminal (EL), intraluminal (IL), and combined IL-EL applicat ion. The effect of cyclooxygenase and nitric oxide synthase inhibition on the insulin response was determined, as was Ca2+ channel involveme nt. Results. EL insulin alone had no significant effect on vessel diam eter. IL insulin produced a dose-dependent dilatation of 5.6%+/-2.9% ( n=22) of the K+ contracted diameter at 200 mu U/ml and up to 12.4%+/-3 .6% (n=22) by 2000 mu U/ml, whereas combined IL-EL insulin application caused dilatation at all concentrations, rising to 15.1%+/-2.9% (n=44 ) at 200 mu U/ml and 19.7%+/-3% (n=44) at 2000 mu U/ml. IL indomethaci n (5x10(-5) M) had no significant effect on the insulin-induced dilata tion, whereas IL L-NAME (10(-4) M) inhibited insulin dilatation comple tely. The addition of EL verapamil (10(-6) M) during insulin-induced d ilatation resulted in further dilatation to 37.8%+/-4.2% (n=18). Howev er, the addition of insulin to verapamil-dilated vessels caused no fur ther dilatation. Exposure to EL insulin while the IL K+ contraction do se-response curve was measured had no effect, Results in main arteries and branches did not differ. Conclusions. The IL application of insul in dilates potassium-contracted pig retinal arteries. This effect was enhanced by the EL presence of insulin, which did not result in dilata tion when it was administered alone. The dilatation response was media ted by nitric oxide but not by prostaglandins. There was some evidence for the involvement of Ca2+ channels in insulin-induced dilatation. T hese results imply that insulin is a vascular regulator in normal cond itions and may have relevance to the vascular changes occurring in dia betes and hypertension in the retina.