En. Su et al., DIRECT VASODILATORY EFFECT OF INSULIN ON ISOLATED RETINAL ARTERIOLES, Investigative ophthalmology & visual science, 37(13), 1996, pp. 2634-2644
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.