Characteristic of NO-cGMP signal pathway in regulation of thoracic aortic relaxation in thyroxine-induced hypertensive rats / 中国药理学通报

ABSTRACT

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.