Fortes Z B, Garcia Leme J, Scivoletto R
Br J Pharmacol. 1983 Jul;79(3):771-81. doi: 10.1111/j.1476-5381.1983.tb10016.x.
The response to vasoactive agents of microvessels in situ and large arteries in vitro was compared in normal and alloxan-diabetic rats. Noradrenaline was equally effective in evoking a constrictor response of mesenteric microvessels in normal and diabetic animals. The constrictor response to a standard amount of noradrenaline in such vessels was fully antagonized by acetylcholine or papaverine, the minimum effective doses being equivalent in normal and diabetic animals. In contrast, the minimum doses of histamine or bradykinin, effective in normal animals, had to be increased about 20 fold to be active in diabetic animals. Increased osmolarity of extracellular fluid caused a significant and equivalent increase in latency of the vasoconstrictor response of microvessels to noradrenaline in normal and diabetic animals. Concentration-effect curves, constructed from the response of isolated aortae to noradrenaline, were similar in normal and diabetic animals, provided the endothelium was removed. Diabetes only affected preparations in which the endothelium was left intact. In these, the median effective concentrations of noradrenaline were greatly increased in comparison with normal values. Precontracted aortae from normal and diabetic animals were equally relaxed by acetylcholine and histamine, provided the endothelium was left intact. Loss of the relaxant response of the preparations in all groups of animals was observed following removal of endothelial cells. It is suggested that different mechanisms may be involved in the effects of vasodilator agents on large arteries in vitro or small vessels in situ. Histamine and bradykinin which are potent permeability-increasing factors, may antagonize the vasoconstrictor response of microvessels to noradrenaline through an action on endothelial cells with increased vascular permeability and temporary changes in composition of extracellular fluid. The reactive process of endothelial cells to permeability factors was affected by diabetes mellitus. However, the response of microvessels to acetylcholine and papaverine which are devoid of permeability-increasing properties, was not influenced by diabetes.
在正常大鼠和四氧嘧啶糖尿病大鼠中，比较了原位微血管和体外大动脉对血管活性药物的反应。去甲肾上腺素在正常和糖尿病动物中诱发肠系膜微血管收缩反应的效果相同。乙酰胆碱或罂粟碱可完全拮抗此类血管对标准量去甲肾上腺素的收缩反应，正常和糖尿病动物的最小有效剂量相当。相比之下，在正常动物中有效的组胺或缓激肽的最小剂量，在糖尿病动物中必须增加约20倍才能发挥作用。细胞外液渗透压升高导致正常和糖尿病动物中微血管对去甲肾上腺素的血管收缩反应潜伏期显著且同等增加。由离体主动脉对去甲肾上腺素的反应构建的浓度-效应曲线，在正常和糖尿病动物中相似，前提是去除内皮。糖尿病仅影响内皮完整的制剂。在这些制剂中，去甲肾上腺素的半数有效浓度与正常值相比大幅增加。如果内皮完整，正常和糖尿病动物预先收缩的主动脉对乙酰胆碱和组胺的舒张程度相同。去除内皮细胞后，所有动物组的制剂均失去舒张反应。提示血管扩张剂对体外大动脉或原位小血管的作用可能涉及不同机制。组胺和缓激肽是强效的增加通透性因子，可能通过作用于血管通透性增加且细胞外液成分发生暂时变化的内皮细胞，拮抗微血管对去甲肾上腺素的血管收缩反应。内皮细胞对通透性因子的反应过程受糖尿病影响。然而，微血管对无增加通透性特性的乙酰胆碱和罂粟碱的反应不受糖尿病影响。
