Hydrogen sulfide defends against the cardiovascular risk of Nw-nitro-L-argininemethyl ester-induced hypertension in rats via the nitric oxide/endothelial nitric oxide synthase pathway

摘要

Background Dyslipidemia caused by liver injury is a significant risk factor for cardiovascular complications.Previous studies have shown that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO),and NO/endothelial nitric oxide synthase (eNOS) pathway is the key route of NO production.The purpose of this study was to investigate whether H2S can ameliorate the high blood pressure and plasma lipid profile in Nw-nitro-L-argininemethyl ester (L-NAME)-induced hypertensive rats by NO/eNOS pathway.Methods Thirty-six 4-week old Sprague-Dawley (SD) male rats were randomly assigned to 6 groups (n=6):control group,L-NAME group,control + glibenclamide group,control + NaHS group,L-NAME + NaHS group,and L-NAME + NaHS + glibenclamide group.Measurements were made of plasma triglycerides (TG),low-density lipoprotein (LDL),high-density lipoprotein (HDL),total cholesterol (CHO),glutamic-pyruvic transaminase (ALT) levels after 5 weeks.Then measurements of NO level and proteins expression of eNOS,P-eNOS,AKT,P-AKT were made in liver tissue.Results After 5 weeks of L-NAME treatment,the blood pressure,plasma TG ((1.22±0.12) mmol/L in L-NAME group vs.(0.68±0.09) mmol/L in control group; P ＜0.05) and LDL ((0.54±0.04) mmol/L in L-NAME group vs.(0.28±0.02) mmol/L in control group; P ＜0.05) concentration were significantly increased,and the plasma HDL ((0.26±0.02) mmol/L in L-NAME group vs.(0.69±0.07) mmol/L in control group; P ＜0.05) concentration significantly decreased.Meanwhile the rats treated with L-NAME exhibit dysfunctional eNOS,diminished NO levels ((1.36±0.09) mmol/g protein in L-NAME group vs.(2.34±0.06) mmol/g protein in control group; P ＜0.05) and pathological changes of the liver.H2S therapy can markedly decrease the blood pressure ((37.25±4.46) mmHg at the fifth week; P ＜0.05),and ameliorate the plasma TG ((0.59±0.06) mmHg),LDL ((0.32±0.04) mmHg),and HDL ((0.46±0.03) mmHg) concentration in L-NAME + NaHS group (all P ＜0.05).H2S therapy can also restore eNOS function and NO bioavailability and attenuate the pathological changes in the liver in L-NAME-induced hypertensive rats.Conclusion H2S protects the L-NAME-induced hypertensive rats against liver injury via NO/eNOS pathway,therefore de.creases the cardiovascular risk.