NO-cGMP信号通路舒张甲亢性高血压大鼠胸主动脉的特性

目的探讨NO-cGMP信号通路舒张甲亢性高血压大鼠胸主动脉的特性。方法大鼠皮下每天注射甲状腺素(T4)0.5 mg.kg-1的剂量或等体积的生理盐水连续16 d,制备甲亢性高血压大鼠模型组和对照组。采用两组大鼠的离体胸主动脉环标本,观察NO供体SNAP对胸主动脉环的影响;利用可溶性鸟苷酸环化酶(sGC)激活剂BAY 41-2272(BAY)、sGC阻断剂ODQ和能透过细胞膜进入胞内而激活蛋白激酶G(PKG)的8-Br-cGMP,观察NO-cGMP信号通路对甲亢性高血压大鼠胸主动脉的舒张作用的影响。结果与对照组相比,甲亢性高血压大鼠体重明显下降而心率、脉压差和收缩压明显升高;SNAP对两组大鼠的胸主动脉环均有明显的舒张作用,但在甲亢性高血压大鼠中的舒张作用明显弱于对照大鼠;用ODQ预处理后,SNAP对两组大鼠胸主动脉环的舒张作用均被阻断;BAY和8-Br-cGMP对两组大鼠的血管环均有明显的舒张作用,但在甲亢性高血压大鼠中的舒张作用明显弱于对照大鼠。结论甲亢性高血压的病理状态下,NO-cGMP信号通路对胸主动脉的舒张作用减弱,且此效应可能与sGC和PKG功能下调有着密切关系。

Characteristic of NO-cGMP signal pathway in regulation of thoracic aortic relaxation in thyroxine-induced hypertensive rats

Aim To explore the characteristic of NO-cGMP signal pathway in the regulation of thoracic aortic relaxation in thyroxine-induced hypertensive rats.Methods Hyperthyroidism was induced by administering Lthyroxine(T4,0.5 mg·kg~-1,sc)daily for 16 days.Sham-treated euthyroid control rats received only vehicle saline for 16 days.SNAP,an NO donor,was used to define the differential relaxation in the thoracic aorta from euthyroid and hyperthyroid rats.To determine the mechanisms involved changes in NO-cGMP signal pathway in the regulation of aortic relaxation from hyperthyroid rats,BAY 41-2272(BAY)was used to activate soluble guanylate cyclase(sGC),ODQ was used to inhibit sGC,and 8-Br-cGMP was used to acti vate protein kinase G(PKG),respectively.Results Thyroid hormone excess for 16 days showed characteristic changes in body weight,heart rate and systolic blood pressure in rats.The body weight was significantly decreased,while heart rate,pulse pressure and systolic blood pressure were increased in T4-treated rats.SNAP caused relaxation in the aorta in both euthyroid and hyperthyroid rats.However,SNAP-induced aortic relaxation was significantly attennuated in hyperthyroid rats than in euthyroid rats.In the presence of ODQ,SNAP-induced aortic relaxation was blocked in both euthyroid and hyperthyroid rats.BAY and 8-BrcGMP-induced aortic relaxation was significantly attennuated in hyperthyroid rats than in euthyroid rats.Conclusion These data suggest that the attenuated effect of NO-cGMP signal pathway is involved in the regulation of aortic relaxation in the pathophysiology of hyperthyroidism,which may be related to the downregulation of sGC and PKG functions.