The Role Of Nitric Oxide And Hydrogen Sulfide In Atorvastatin Calcium’s Antiatherogenic Course

Objective： To observe the changes of serous nitric oxide （NO） and hydrogensulfide （H₂S） systems in atherosclerotic rats, to survey the effects of atorvastatincalcium to serous NO and H₂S systems in atherosclerotic rats, to explore for thefirst time the influence of blockage of H₂S passageway on atorvastatin calcium’santiatherogenic course, to research the influence of blockage of NO passageway onatorvastatin calcium’s antiatherogenic course, to survey the interaction betweenNO system and H₂S system in atorvastatin calcium’s antiatherogenic course.Methods:60sanitary healthy male wistar rats, weighted180to220gram,were randomly divided into5groups according to body weight: control group, HFgroup, HF+ATV group, HF+ATV+PPG group and HF+ATV+L-NAME group,each group with12rats. All rats were bred for12weeks. Control group were fedwith normal rat diet persistently; HF group, HF+ATV group, HF+ATV+PPG groupand HF+ATV+L-NAME group were fed with high fat diet persistently, and weregiven vitamin D₃（700000IU/kg） through peritoneal injection at the beginning of1^st,5^th and9^th week respectively; control group and HF group were givenphysiological saline （1².5ml/day） via intragastric administration, were givenphysiological saline （0.2⁰.5ml/day） via peritoneal injection during9^th to12^th week; HF+ATV group were given atorvastatin calcium （5mg/kg/day） viaintragastric administration, were given physiological saline （0.2⁰.5ml/day） viaperitoneal injection during9^th to12^th week; HF+ATV+PPG group were givenatorvastatin calcium （5mg/kg/day） via intragastric administration, were given PPG（37.5mg/kg/day） via peritoneal injection during9^th to12^th week; HF+ATV+L-NAME group were given atorvastatin calcium （5mg/kg/day） via intragastricadministration, were given L-NAME （15mg/kg/day） via peritoneal injection during9^th to12^th week. At the end of12^th week, we collected blood sample from the heart,got the arch of aorta and aorta descendens, assayed blood fat with fully automaticbiochemical analysator, made HE stain of the arch of aorta, determined the quantity of serous NO and the vitality of serous total nitric oxide synthase （T-NOS）,detected the quantities of serous eNOS, H₂S and CSE by ELISA, assayed theexpression of eNOSmRNA and CSEmRNA in aorta descendens by RT-PCR.Results: Compared with control group, the serous total cholesterol （TC）,triglyeride （TG） and low-density lipoprotein cholesterol （LDL-C） of HF groupwere higher （P<0.05）, there was typical atherosclerosis in the aorta, the quantitiesof serous NO, eNOS, H₂S, CSE and the vitality of T-NOS were lower （P<0.05）, theexpression of eNOSmRNA and CSEmRNA in aorta descendens declinedremarkably （P<0.05）. Compared with HF group, the quantities of serous TC andLDL-C in HF+ATV group were lower （P<0.05）, there was milder atherosclerosisin the aorta, the quantities of serous NO, eNOS and the expression of eNOSmRNAin aorta descendens were higher （P<0.05）, the quantities of serous H₂S and CSEhad no significant change （P>0.05）. Compared with HF+ATV group, there was nosignificant change of blood fat in HF+ATV+PPG group （P>0.05）, but thequantities of serous H₂S and CSE were lower （P<0.05）, and the quantities of serousNO and eNOS and the expression of eNOSmRNA in aorta descendens were higher（P<0.05）. Compared with HF+ATV group, the serous of TC and LDL-C inHF+ATV+L-NAME group were higher （P<0.05）, the quantities of serous NO,eNOS and the vitality of T-NOS were lower （P<0.05）, but the quantities of serousH₂S, CSE and the expression of CSEmRNA in aorta descendens were higher（P<0.05）.Conclusions: Atorvastatin calcium could raise the quantities and vitality ofserous NO system in atherosclerotic wistar rats, had no significant influence onserous H₂S system. Blockade of NO passageway in rats significantly weakenedatorvastatin calcium’s antiatherogenic effects, but blockade of H₂S passageway hadno remarkable influence. In the course of treating atherosclerotic rats withatorvastatin calcium, if NO system or H₂S system were blocked, there would becompensatory increase of the quantity of the other system.