Abstract:Objective:To observe the effects and study the mechanisms of slow-releasing hydrogen sulfide donor GYY4137 on the vasodilation of thoracic aortic in spontaneously hypertensive rats (SHRs). Methods:Male SHRs at 12 weeks of age were randomly divided into 4 groups treated with different dosages of GYY4137:0(SHR group),10(GYY10 group),25(GYY25 group)or 50(GYY50 group)mg/kg/day. GYY4137 was given by intraperitoneal injection once daily for 4 weeks. Age-matched normotensive Wistar-Kyoto(WKY)rats served as controls (WKY group). SHR and WKY control groups received the same volume of physiological saline. During treatment,systolic blood pressure (SBP)was measured by the tail-cuff method. After 4 weeks,vasodilation of thoracic aortic was measured. The degree of oxidative stress was evaluated by DHE staining,malondialdehyde (MDA)and total antioxidant capacity(T-AOC). The expression of p85α,Akt,p-Akt(Ser473),eNOS and p-eNOS(Ser1177)was detected by western blot. Results:After treatment,GYY4137 improved endothelium-dependent vasodilation of thoracic aortic in SHRs,lessened the superoxide generation,decrease MDA level,enhanced T-AOC,and increased the protein level of p85α and the phosphorylation of Akt and eNOS. Conclusion:GYY4137 improved endothelium-dependent vasodilation of SHRs,which may be associated with the suppression of oxidative stress and activation of PI3K/AKT/eNOS signal pathway.