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短期和长期糖尿病大鼠离体肠系膜阻力动脉和基底动脉的血管反应。

Vascular responses of isolated mesenteric resistance and basilar arteries from short- and long-term diabetic rats.

作者信息

Van Buren T, Vleeming W, Krutzen M M, Van de Kuil T, Gispen W H, De Wildt D J

机构信息

Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Medical Faculty, Utrecht University, The Netherlands.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1998 Dec;358(6):663-70. doi: 10.1007/pl00005309.

Abstract

Vascular dysfunctions, e.g. alterations in the reactivity of blood vessels to neurotransmitters and hormones, are a well-established complication of diabetes mellitus. Whether these impairments are a consequence of direct postsynaptic deficits and/or indirect presynaptic deficits remains to be determined. To this end, we investigated the influence of the duration of diabetes on relaxation and contraction responses of isolated mesenteric resistance and equally-sized basilar arteries to postsynaptic activation by various vasoactive agents, using streptozotocin-induced diabetic rats and age-matched controls. Relaxation responses to vasodilator agents were studied in KCl-precontracted arteries. The duration of diabetes (4 or 40 weeks) did not affect the vasodilator responses to sodium nitroprusside or salbutamol in either artery. In mesenteric resistance vessels from short-term (4 weeks) and long-term (40 weeks) diabetic rats the vasoconstrictor responses to KCI, serotonin and vasopressin were the same as those in non-diabetic rats; however, the sensitivity (EC50) to noradrenaline was slightly but significantly enhanced after the long-term diabetic state. In contrast to the mesenteric arteries, noradrenaline did not cause contraction in basilar arteries taken from diabetic and control rats. Thus, there appear to be important differences in the reactivity to noradrenaline of the peripheral and cerebral vasculature. The basilar artery from short-term and long-term diabetic rats did not show different responsiveness to vasopressin whereas to serotonin a significant enhanced and decreased sensitivity (EC10 and EC50) was demonstrated in short-term and long-term diabetes, respectively. Our findings indicate that postsynaptic impairments do not play a major role in the alterations of vasoreactivity to vasodilators, noradrenaline or vasopressin seen in experimental diabetes. However, the duration of the diabetic state may have serious consequences for vasoreactivity of basilar arteries to serotonin and, therefore, warrants further investigations.

摘要

血管功能障碍,例如血管对神经递质和激素反应性的改变,是糖尿病公认的并发症。这些损害是直接的突触后缺陷和/或间接的突触前缺陷的结果,仍有待确定。为此,我们使用链脲佐菌素诱导的糖尿病大鼠和年龄匹配的对照,研究了糖尿病持续时间对分离的肠系膜阻力动脉和同等大小的基底动脉对各种血管活性药物突触后激活的舒张和收缩反应的影响。在氯化钾预收缩的动脉中研究了对血管舒张剂的舒张反应。糖尿病持续时间(4周或40周)对任一动脉对硝普钠或沙丁胺醇的血管舒张反应均无影响。在短期(4周)和长期(40周)糖尿病大鼠的肠系膜阻力血管中,对氯化钾、5-羟色胺和血管加压素的血管收缩反应与非糖尿病大鼠相同;然而,长期糖尿病状态后对去甲肾上腺素的敏感性(EC50)略有但显著增强。与肠系膜动脉相反,去甲肾上腺素不会引起糖尿病大鼠和对照大鼠基底动脉的收缩。因此,外周和脑血管系统对去甲肾上腺素的反应性似乎存在重要差异。短期和长期糖尿病大鼠的基底动脉对血管加压素的反应性没有差异,而对5-羟色胺的敏感性在短期和长期糖尿病中分别显著增强和降低(EC10和EC50)。我们的研究结果表明,突触后损伤在实验性糖尿病中对血管舒张剂、去甲肾上腺素或血管加压素的血管反应性改变中不起主要作用。然而,糖尿病状态的持续时间可能对基底动脉对5-羟色胺的血管反应性产生严重影响,因此值得进一步研究。

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