胰岛素对离体视网膜小动脉的直接血管舒张作用。

Direct vasodilatory effect of insulin on isolated retinal arterioles.

作者信息

Su E N, Yu D Y, Alder V A, Cringle S J, Yu P K

机构信息

Lions Eye Institute, University of Western Australia, Nedlands, Australia.

出版信息

Invest Ophthalmol Vis Sci. 1996 Dec;37(13):2634-44.

PMID:8977477

Abstract

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 were dissected, cannulated, and perfused. Vessel diameter was measured continuously on-line. Vessels were precontracted to 66% +/- 0.9% (SEM, n = 148) of their original diameter by perfusing with 124 mM K(+)-Krebs solution. Dose-response curves to insulin (2 to 2000 microU/ml) were compared for extraluminal (EL), intraluminal (IL), and combined IL-EL application. The effect of cyclooxygenase and nitric oxide synthase inhibition on the insulin response was determined, as was Ca2+ channel involvement.

RESULTS

EL insulin alone had no significant effect on vessel diameter. IL insulin produced a dose-dependent dilatation of 5.6% +/- 2.9% (n = 22) of the K+ contracted diameter at 200 microU/ml and up to 12.4% +/- 3.6% (n = 22) by 2000 microU/ml, whereas combined IL-EL insulin application caused dilatation at all concentrations, rising to 15.1% +/- 2.9% (n = 44) at 200 microU/ml and 19.7% +/- 3% (n = 44) at 2000 microU/ml. IL indomethacin (5 x 10(-5) M) had no significant effect on the insulin-induced dilatation, whereas IL L-NAME (10(-4) M) inhibited insulin dilatation completely. The addition of EL verapamil (10(-6) M) during insulin-induced dilatation resulted in further dilatation to 37.8% +/- 4.2% (n = 18). However, the addition of insulin to verapamil-dilated vessels caused no further dilatation. Exposure to EL insulin while the IL K+ contraction dose-response curve was measured had no effect. Results in main arteries and branches did not differ.

CONCLUSIONS

The IL application of insulin dilates potassium-contracted pig retinal arteries. This effect was enhanced by the EL presence of insulin, which did not result in dilatation when it was administered alone. The dilatation response was mediated by nitric oxide but not by prostaglandins. There was some evidence for the involvement of Ca2+ channels in insulin-induced dilatation. These results imply that insulin is a vascular regulator in normal conditions and may have relevance to the vascular changes occurring in diabetes and hypertension in the retina.

摘要

目的

验证胰岛素对视网膜动脉及其分支具有直接血管舒张作用这一假说，并研究其相关机制。

方法

解剖猪视网膜动脉段，插管并进行灌注。在线连续测量血管直径。通过灌注124 mM K⁺ - Krebs溶液将血管预收缩至其原始直径的66%±0.9%（标准误，n = 148）。比较胰岛素（2至2000 μU/ml）经腔外（EL）、腔内（IL）以及联合IL - EL应用时的剂量 - 反应曲线。测定环氧合酶和一氧化氮合酶抑制对胰岛素反应的影响，以及Ca²⁺通道的参与情况。

结果

单独的腔外胰岛素对血管直径无显著影响。腔内胰岛素在200 μU/ml时使K⁺收缩直径产生5.6%±2.9%（n = 22）的剂量依赖性扩张，至2000 μU/ml时可达12.4%±3.6%（n = 22），而联合IL - EL应用胰岛素在所有浓度下均引起扩张，在200 μU/ml时升至15.1%±2.9%（n = 44），在2000 μU/ml时为19.7%±3%（n = 44）。腔内吲哚美辛（5×10⁻⁵ M）对胰岛素诱导的扩张无显著影响，而腔内L - NAME（10⁻⁴ M）完全抑制胰岛素扩张。在胰岛素诱导扩张期间添加腔外维拉帕米（10⁻⁶ M）导致进一步扩张至37.8%±4.2%（n = 18）。然而，在维拉帕米扩张的血管中添加胰岛素未引起进一步扩张。在测量腔内K⁺收缩剂量 - 反应曲线时暴露于腔外胰岛素无影响。在主要动脉和分支中的结果无差异。