Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100, Sihhiye, Ankara, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2011 May;383(5):509-17. doi: 10.1007/s00210-011-0601-6. Epub 2011 Mar 11.
Hydrogen sulfide (H₂S) is an endogenous gas which has potent relaxant effect in vascular and nonvascular smooth muscles. In the present study, we have investigated how streptozotocin (STZ)-induced diabetes affected the relaxant effect of H₂S in rat isolated thoracic aorta and mesenteric and pulmonary arteries. Diabetes was induced by IV injection of STZ (35 mg/kg). Insulin treatment was applied by using insulin implants. At the end of 4 and 12 weeks, the thoracic aorta and mesenteric and pulmonary arteries were isolated, and the relaxation responses to sodium hydrogen sulfide (NaHS), diazoxide, and acetylcholine were evaluated. The mRNA and protein levels of H₂S-synthesizing enzymes were also examined by RT-PCR and Western Blot. The relaxation response to NaHS in the arteries isolated from both 4 and 12 week-diabetic rats was increased when compared with that obtained from the control group. Glibenclamide inhibited the relaxation response to NaHS in the arteries isolated from either diabetic or non-diabetic group of rats. Concurrent treatment of insulin to STZ-injected rats prevented the potentiation of the relaxant effect of NaHS in the arteries. However, acetylcholine and diazoxide-induced relaxation responses were not altered in diabetic group of rats. The mRNA and protein levels of H₂S-synthesizing enzymes were also not altered in diabetic rats. STZ-induced experimental diabetes in rats resulted in the potentiation of the relaxation response to H₂S in vascular tissues. The potentiated relaxation to H₂S in diabetic arteries may play a role in vascular complications frequently seen in severe diabetes.
硫化氢（H₂S）是一种内源性气体，对血管和非血管平滑肌具有强烈的舒张作用。在本研究中，我们研究了链脲佐菌素（STZ）诱导的糖尿病如何影响大鼠离体胸主动脉、肠系膜和肺血管中 H₂S 的舒张作用。糖尿病通过 IV 注射 STZ（35mg/kg）诱导。使用胰岛素植入物进行胰岛素治疗。在第 4 和 12 周结束时，分离胸主动脉、肠系膜和肺血管，并评估对 NaHS、二氮嗪和乙酰胆碱的舒张反应。还通过 RT-PCR 和 Western Blot 检查 H₂S 合成酶的 mRNA 和蛋白水平。与对照组相比，来自 4 周和 12 周糖尿病大鼠的动脉对 NaHS 的舒张反应增加。格列本脲抑制来自糖尿病或非糖尿病大鼠组的动脉对 NaHS 的舒张反应。同时用胰岛素处理 STZ 注射大鼠可防止 NaHS 舒张作用的增强。然而，糖尿病大鼠的乙酰胆碱和二氮嗪诱导的舒张反应没有改变。糖尿病大鼠的 H₂S 合成酶的 mRNA 和蛋白水平也没有改变。STZ 诱导的大鼠实验性糖尿病导致血管组织对 H₂S 舒张反应增强。糖尿病动脉中 H₂S 舒张作用的增强可能在严重糖尿病中经常出现的血管并发症中发挥作用。
