Frøbert Ole, Bagger Jens P, Simonsen Ulf, Lund Sten, Gravholt Claus H
Department of Cardiology S, Aalborg University Hospital, DK-900 Aalborg, Denmark.
Clin Sci (Lond). 2004 Aug;107(2):213-20. doi: 10.1042/CS20040006.
In acute ischaemia, glucose-insulin-potassium administration reduces mortality and beta-adrenoceptor antagonists have favourable effects on the outcome of ischaemic heart disease. The present study was designed to investigate whether insulin (1.4x10(-7) M) and the beta-adrenoceptor antagonist, propranolol (10(-5) M), increase hypoxic vasodilation in correspondence with changes in glycolysis. Porcine coronary arteries, precontracted with 10(-5) M prostaglandin F(2alpha), were mounted in a pressure myograph and a microdialysis catheter was inserted in the tunica media. Hypoxic vasodilation, interstitial lactate/pyruvate ratio and interstitial glucose were measured at low (2 mM) and high (20 mM) glucose concentrations. Hypoxia (60 min) caused vasodilation and doubled the lactate/pyruvate ratio. Treatment with insulin quadrupled the lactate/pyruvate ratio during hypoxia, but did not change hypoxic vasodilation. Propranolol blocked isoprenaline-evoked vasodilation, but hypoxic increases in lactate/pyruvate ratio and vasodilation did not change. The combination of insulin and propranolol did not cause further changes compared with each drug added alone, although the combination increased vasoconstriction during reoxygenation. Interstitial glucose fell during hypoxia at an organ bath glucose concentration of 2 mM, and rose at a glucose concentration of 20 mM. Addition of insulin and propranolol alone or in combination had no effect on interstitial glucose concentration. Accordingly, arteries were found to contain only minute amounts of the glucose transporter isoform GLUT4. Our findings suggest that insulin increases arterial glycolysis, but treatment with insulin, propranolol, or both, is not associated with enhanced coronary vasodilation during hypoxia.
在急性缺血时，给予葡萄糖 - 胰岛素 - 钾可降低死亡率，β - 肾上腺素能受体拮抗剂对缺血性心脏病的预后有有利影响。本研究旨在调查胰岛素（1.4×10⁻⁷ M）和β - 肾上腺素能受体拮抗剂普萘洛尔（10⁻⁵ M）是否会随着糖酵解变化增加缺氧性血管舒张。用10⁻⁵ M前列腺素F₂α预收缩的猪冠状动脉安装在压力肌动描记仪中，并在中膜插入微透析导管。在低（2 mM）和高（20 mM）葡萄糖浓度下测量缺氧性血管舒张、组织间乳酸/丙酮酸比值和组织间葡萄糖。缺氧（60分钟）导致血管舒张并使乳酸/丙酮酸比值加倍。胰岛素治疗使缺氧期间的乳酸/丙酮酸比值增加了四倍，但并未改变缺氧性血管舒张。普萘洛尔阻断异丙肾上腺素引起的血管舒张，但缺氧时乳酸/丙酮酸比值和血管舒张的增加并未改变。与单独添加每种药物相比，胰岛素和普萘洛尔联合使用未引起进一步变化，尽管联合使用在复氧期间增加了血管收缩。在器官浴葡萄糖浓度为2 mM时，缺氧期间组织间葡萄糖下降，而在葡萄糖浓度为20 mM时升高。单独或联合添加胰岛素和普萘洛尔对组织间葡萄糖浓度无影响。因此，发现动脉中仅含有微量的葡萄糖转运体异构体GLUT4。我们的研究结果表明，胰岛素可增加动脉糖酵解，但胰岛素、普萘洛尔或两者联合治疗与缺氧期间冠状动脉血管舒张增强无关。
