Combined antihypertensive effect of GSY and metoprolol,based on endothelium-dependent vasodilatation function

OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).

Combined anti-hyperuricemia effect of Di.E and Gpm.E on hyperuricemia rats induced by high-purine diet

OBJECTIVE Di.E and Gpm.E were separately extracted from two kinds of traditional Chinese medicine.The aim of this research is to investigate the combined anti-hyperuricemia effect of Di.E and Gpm.E on hyperuricemia rats induced by high-purine diet,and to study the underlying mechanism.METHODS Sprague Dawley(SD)rats were divided into some groups according to their serum uric acid(UA),the normal control group received standard diet,while others were fed with high-purine diet.After the success of modeling,SD rats were divided into 5groups according to UA:normal control group,model control group,Di.E and Gpm.E(high,middle,low dosages).The treatment groups were simultaneously orally administered.Two days before the last administration,the urine N-acetyl beta-D Glucosaminidase(NAG),Lysozyme(LYS)activity were separately detected using the urine collected from metabolic cage for 24 h.After the last administration,the blood was taken from postcava to detect the level:① The related indexes of liver and kidney function:the serum UA,blood urea nitrogen(BUN),creatinine(CR),alanine aminotransferase(ALT);② The uric acid metabolism related enzymes:the serum and liver xanthine oxidase(XOD),adenosine deaminase(ADA),guanine deaminase(GD),xanthine dehydrogenase(XDH)activity;③ Fibrosis related indexes of renal tissue:connective tissue growth factor(CTGF),monocyte chemotactic protein-1(MCP-1),TGF-β1,TNF-α,NF-κB levels.RESULTS Di.E and Gpm.E(high,middle dosages)could markedly reduce the serum UA level significantly,also can decrease XOD,ADA,TNF-α,MCP-1,NF-κB activity significantly.CONCLUSION The results show that Di.E and Gpm.E can decrease the serum UA level significantly,improve the liver and kidney function and slow down the process of renal fibrosis;the therapeutic effects may be related to their inhibition of XOD,ADA activity.