Effect of Ramipril on Renin-Angiotensin-Aldosterone System of Young and Middle-Aged Patients with Hypertension

Objective:To explore the effect of Ramipril on renin-angiotensin-aldosterone system of young and middle-aged patients with hypertension.Methods 90 young and middle-aged patients with hypertension who had been seeking treatment in the hospital between August 2017 and August 2018 were selected and randomly divided into a control group and an observation group according to the random number table,with 45 cases in each group.The control group received Amlodipine for treatment,whereas the observation group was given Amlodipine combined with Ramipril for treatment.The hemodynamic indexes,blood lipid,blood pressure,angiotensinⅡ(AngⅡ),plasma renin(PRA),aldosterone(ALD)levels and incidence of adverse reactions during the medication in the two groups were compared before and after treatment.Results After treatment,thefibrinogen,plasma viscosity and whole blood viscosity in the observation group were significantly higher than those in the control group,with statistically significant difference between the two groups(P<0.05);total cholesterol(TC),triacylglycerol(TG)and low density lipoprotein cholesterin(LDL-C)in the observation group were significantly lower than those in the control group,and statistically significant difference was registered between the two groups(P<0.05);the diastolic pressure and systolic pressure in the observation group were decreased more significantly compared with the control group,with statistically significant difference shown between the two groups(P<0.05);the AngⅡ,ALD and PRA levels in the observation group were significantly lower than the control group,and the difference between two groups were statistically significant(P<0.05);during the medication,no significant bleeding or liver and kidney function damages occurred in the two groups.Conclusions For young and middle-aged patients with hypertension,the treatment with Ramipril,which is of high safety,can effectively improve the activity of their renin-angiotensin-aldosterone system,reduce the level of blood pressure and AngⅡ,ALD and PRA levels.

Relationship of renin-angiotensin-aldosterone system activity with systemic inflammatory response and target organ function in patients with severe acute pancreatitis

Objective:To study the relationship of renin-angiotensin-aldosterone system (RAAS) activity with systemic inflammatory response and target organ function in patients with severe acute pancreatitis.Methods: The patients with acute pancreatitis admitted in Zigong Third People's Hospital between June 2014 and December 2016 were selected and divided into MAP group and SAP group, and the healthy volunteers who received physical examination during the same period and were with matched general data were selected as control group. Serum was collected to determine the levels of RAAS molecules, inflammation molecules as well as liver and intestinal mucosal barrier injury molecules.Results: Serum PRA, AngII, ALD, TNF-α, sTREM-1, PCT, CRP, LPS, DAO and HBD2 contents of SAP group and MAP group were significantly higher than those of control group;serum PRA, AngII, ALD, TNF-α, sTREM-1, PCT, CRP, LPS, DAO and HBD2 contents of SAP group were significantly higher than those of MAP group;serum PRA, AngII and ALD contents of SAP group were positively correlated with TNF-α, sTREM-1, PCT, CRP, LPS, DAO and HBD2 contents.Conclusion:The activation of RAAS system in patients with severe acute pancreatitis is closely related to the amplification of systemic inflammatory response and the damage of target organs.

Research progress on gene polymorphisms related to the renin-angiotensin-aldosterone system and essential hypertension

Background Essential hypertension(EH)is a complex polygenic genetic disease,which is the result of the interaction of multiple genetic factors,environmental factors,and risk factors.The susceptibility of inherited genes is an important risk factor for EH,and pathogenic genes and susceptibility loci can promote EH formation.It has been found that renin-angiotensin angiotensin aldosterone system(RAAS)genes are involved in most physiological regulation in humans,especially with EH.Its gene polymorphisms and EH susceptibility are current research hotspots.Therefore,this article reviewed the research on the correlation between angiotensinogen(AGT),angiotensin-converting enzyme(ACE),angiotensin II.receptor type 1(AGTR1),aldosterone synthetase(CYP11B2),and beta 1-adrenergic receptor(ADRB1)gene with EH,respectively.[S Chin J Cardiol 2024;25(3):193-199]

Genetic polymorphisms of the renin-angiotensin-aldosterone system in Chinese patients with end-stage renal disease secondary to IgA nephropathy

Background Genetic variability in the renin-angiotensin-aldosterone system may modify renal responses to injury and disease progression. The angiotensin I-converting enzyme （ACE） gene insertion/deletion （I/D）, the angiotensinogen （AGT） gene, M235T, the aldosterone synthase （CYP11B2） gene, C-344T, and the angiotensin II type 1 receptor （AT1R） gene, Al166C, have been shown to be associated with IgA nephropathy （IgAN） and its progression. We determined the presence of these polymorphisms in 130 Chinese patients with IgAN, including 47 patients with end-stage renal disease （ESRD） and 120 healthy Chinese subjects, to assess their impact on the susceptibility to disease and the liability of progression to ESRD. Methods Genotyping was performed with DNA isolated from peripheral leucocytes using polymerase chain reaction amplification of the polymorphic sequence, restriction enzyme digestion, and separation and identification of DNA fragments. Clinical data from renal biopsies were collected. Results ACE, AGT, CYP and AT1R genotype distributions were similar in patients with IgAN and in controls. Comparing patients with ESRD （IgAN-ESRD） and those without ESRD （IgAN-non ESRD）, there was a significant increase only in the ACE DD genotype （P 〈0.05） among the four gene polymorphisms. There was significant dominance of the male （P 〈0.05）, more marked hypertension （P 〈0.01）, proteinuria （P 〈0.01） and increased serum creatinine during renal biopsy （P〈0.01） in the IgAN-ESRD group. Conclusion Among the ACE, AGT, ATIR and CYP gene polymorphisms, only the DD genotype may predispose the individual to increased risk of progression to ESRD in the Chinese population.

Dual Blockade of the Renin-angiotensin-aldosterone System in Type 2 Diabetic Kidney Disease

Objective： To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system （RAAS） among patients with type 2 diabetic kidney disease. Data Sources： We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use ofmonothempy, without applying any language restrictions. Keywords for the searches included ＂＇diabetic nephropathy,＂ ＂chronic kidney disease,＂ ＂chronic renal insufficiency,＂ ＂diabetes mellitus,＂ ＂dual therapy,＂ ＂combined therapy,＂ ＂dual blockade,＂ ＂renin-angiotensin system,＂ ＂angiotensin-converting enzyme inhibitor,＂ ＂angiotensin-receptor blocker,＂ ＂aldosterone blockade,＂ ＂selective aldosterone blockade,＂ ＂renin inhibitor,＂ ＂direct renin inhibitor,＂ ＂mineralocorticoid receptor blocker,＂ etc. Study Selection： The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus. Results： Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin I I receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons. Conclusions： Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted to study the combination therapy as an evidence-based practice.

Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensinaldosterone system

Background Obstructive sleep apnea （OSA） is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system （RAAS）. We meta-analyzed the effects of OSA on plasma levels of RAAS components. Methods Full-text studies published on MEDL1NE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index 〉 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the 12 statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. Results The meta-analysis included 13 studies, of which 10 reported results on renin （n = 470 cases and controls）, 7 on angiotensin II （AnglI, n = 384）, and 9 on aldosterone （n = 439）. AnglI levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI： 2.00-4.79, P 〈 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension （mean differences = 1.32 ng/dL, 95% CI： 0.58-2.07, P = 0.0005）. Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL （95% CI： 0.88-1.82, P 〈 0.00001） emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. Conelusions OSA is associated with higher AnglI and aldosterone levels, espe- cially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity.

ACEI attenuates the progression of CCl_4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

AIM： Angiotensin II has pro-fibrotic function in the liver. Blockade of the renin-angiotensin-aldosterone-system （RAAS） attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensin-converting enzyme inhibitor （ACEI） on the progression of rat hepatic fibrosis. METHODS： Forty male Wistar rats were divided into three groups. Model group （Mo）： The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group （Pe）： The rats were injected subcutaneously with 40% of CCl4. Perindopril, equivalent to 2 mg/（kg·d）, was administrated. Control group （Nc）： the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed. The liver sections were stained with Masson. The protein expressions of ATIR, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB （NF-κB） DNA binding activity was examined by EMSA （Electrophoretic gel mobility shift assay）. Matrix metalloproteinase-2,9 （MMP-2,9） activity was assessed by zymography. Serum laminin （LN） and hyaluronic acid （HA） were measured using radioimmunoassays. RESULTS： Using Western blot, we clearly provided direct evidence for the expression of ATIR in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score, protein levels of ATIR, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA bindingactivity markedly increased in model group, perindopril treatment considerably reduced NF-κB DNA binding activity.CONCLUSION： Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB, NF-BB and MMP-2,9.

Liver cirrhosis and arterial hypertension

Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems （renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin）, and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin generelated peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective （although relative） counterbalance to increased arterial blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension （essential, secondary） may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most likely includes the combination of vasodilatation and vasoconstriction in parallel.

Cardiovascular and cerebrovascular outcomes in elderly hypertensive patients treated with either ARB or ACEI

Background Although angiotensin converting enzyme inhibitors （ACEI） and angiotensin receptor blockers （ARB） are equally important in the treatment of hypertension, there is less evidence whether they have equal cardiovascular and cerebrovascular protective effects, especially in elder hypertensive patients. This study aims to clarify this unresolved issue. Methods This cross-sectional study included clinical data on 933 aged male patients with hypertension who received either an ARB or ACEI for more than two months between January 2007 and May 2011. The primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints were unstable angina, new atrial fibrillation, and transient ischemic attack. Results The median follow-up time was 24 months. Age, drug types, cerebral infarction history, renal dysfunction history were the independent predictors of the primary endpoint. The risk of an occurrence of a primary endpoint event was higher in the ARB group than the ACEI group [P = 0.037, hazard ratios （HR）： 2.124, 95% confidence interval （95% CI）： 1.048-4.306]. The Kaplan-Meier method also suggests that the rate of primary endpoint occurrence was higher in the ARB group than the ACEI group （P = 0.04）. In regard to the secondary endpoints, there were no significant differences between the two treatment arms （P = 0.137, HR： 1.454, 95% CI： 0.888-2.380）. Patient age and coronary heart disease history were independent predictors of the secondary endpoint. Conclusion ACEI were more effective than ARB in reducing cardiovascular and cerebrovascular morbidity and mortality in aged patients with hypertension.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.

Mechanism of Pingyang Jiangya Formula in treating hypertension based on network pharmacology and in vivo study

Objective This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula(平阳降压方,PYJYF)in treating hypertension,based on network pharmacology,and to verify the subsequent predictions through animal experiments.Methods The active components and related target genes of PYJYF were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM),Encyclopedia of Traditional Chinese Medicine(ETCM),and Drug Bank databases and available literature.The hypertension target genes were screened based on Therapeutic Target Database(TTD),GeneCards,Online Mendelian Inheritance in Man(OMIM),UniProt,and relevant literature.The component-disease-target network intersection target genes were inputted into the STRING database,and the key target genes were selected according to the degree algorithm.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to explore the multitarget mechanism of action and molecular regulatory network of PYJYF in the treatment of hypertension.To verify this prediction,we used PYJYF to intervene in spontaneously hypertensive rats(SHRs)and Wistar–Kyoto rats(WKY)as normal control,and the noninvasive tail artery manometry method was used to measure systolic blood pressure(SBP)in the rat tail before PYJYF intervention.After drug intervention,the SBP of each group rats were measured and compared every week.Enzyme-linked immunosorbent assay(ELISA)was used to test plasma renin,angiotensin II(Ang II),and aldosterone(Ald)levels,and hematoxylin-eosin(HE)staining was used to observe pathological damage to the renal vessels in each group of rats.Western blot and reverse transcription real-time quantitative PCR(RT-PCR)were used to detect the protein and mRNA expression levels of PI3 K,AKT1,BAX,and Bcl-2,respectively.Results A total of 4123 hypertension targets were obtained from related databases.From the TCMSP and chemical databases,78 active components of PYJYF and the corresponding 401 drug targets were retrieved.Data analysis revealed that 208 drug targets directly interacted with the hypertension targets in PYJYF.The 10 targets most closely related to hypertension target proteins in PYJYF were directly retrieved from relevant databases.GO analysis revealed that 10 direct target proteins were involved in all aspects of the antihypertensive effects of PYJYF,as well as molecular biological processes,such as the regulation of blood pressure,renin-angiotensin-aldosterone system(RAAS),angiotensin-mediated ligand reactions,and biological stimulation of cardiomyocyte apoptosis.KEGG pathway enrichment analysis revealed that PYJYF directly affected 20 signaling pathways associated with hypertension.In animal experiments,PYJYF reduced the protein and m RNA levels of PI3 K,Akt,and Bax and upregulated the expression of the protein and m RNA levels of Bcl-2,reduced plasma renin,Ang II,and Ald levels,improved the hyperactivity of RAAS,and significantly reduced SBP in SHRs.Conclusion PYJYF is effective for hypertension therapy that acts through multiple compounds and targets.The possible underlying molecular mechanism includes regulating the PI3 K/Akt signaling pathway to suppress RAAS,increasing the ratio of Bcl-2/Bax proteins,and inhibiting apoptosis,thereby mediating the repair of renal and renal vascular damage caused by hypertension.These findings warrant further research for use in clinical settings.

Nonalcoholic fatty liver disease and the renin-angiotensin system:Implications for treatment

Nonalcoholic fatty liver disease(NAFLD) is the commonest liver disease in Western countries.Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far.Emerging evidence,mainly from animal studies,suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors(ACE-I) and angiotensin receptor blockers(ARBs) as a potentially useful therapeutic approach.However,data from human studies are limited and contradictory.In addition,there are few randomized controlled trials(RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies,pilot prospective studies and post hoc analyses of clinical trials.Accordingly,more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD.

The effects and mechanisms of total flavonoids of Cydonia oblonga Mill. on myocardial hypertrophy in spontaneously hypertensive rats

Aim To study the activity and mechanism of inhibition of myocardial hypertrophy of total flavonoids of Cydonia oblonga Mill. in spontaneously hypertensive rats. Methods Total flavonoids of COM （COMF） were sepa- rated and purified by the optimal process. SHtl were divided into 6 groups： SHR control group （SHR） , captopril group （SHR ＋ CAP, 25 μg · g^-1）, Eucommia ulmoides Oliver group （SHR ＋ EUO, 30 μg · g^-1）, low （SHR ＋ COMF-L, 40 μg · g^-1） ,middle （SHR ＋ COMF-M, 80 μg· g^-1） and high dose （SHR ＋ COMF-H, 160 μg · g^-1） of COMF groups. Wistar-Kyoto （WKY） rats （n= 8 ） were given distilled water as control The drugs were given by intragastric administration for 16 weeks. The histological and pathological examination of the heart were performed and organic damage were valued. The levels of Ang II and ALD in blood and heart were evaluated. The mRNA and protein expression of ACE, ACE2 and AT~ was determined by RT-PCR and Western blot to evaluate the effect of COMF on RAAS. Results Compared with SHR control group, HW, HW/BW, LVM and LVM/BW de- creased in SHR ＋ COMF-M and SHR ＋ COMF-H groups; Cadiomyocyte hypertrophy was inhibited in COMF groups; The concentration of Ang 11 and ALD in heart and blood decreased; ACE and AT1 mRNA and protein ex- pression in heart tissue decreased while ACE2 mRNA expression increased （P 〈 0.01 or P 〈 0.05） , Conclusion Total flavonoids of Cydonia oblonga Mill. showed the effect of inhibition of myocardial hypertrophy in spontaneously hypertensive rats and the mechanism was related to. inhibit the activity of Renin-angiotensin-aldosterone system.

Effects of highly potent atrial natriuretic peptide on circulating reninangiotensin-aldosterone system and cardiac function in dogs with ischemic heart failure

The effects of highly-potent atrial natriuretic peptide (HPANP) on circulating re nin-angiotensin-aldos-terone system (RAAS) and cardiac function were studied in an acute ischemic heart failure model. HPANP (6 μg/kg and 3 μg/kg) was infused intracoronarily. It was found that both doses of HPANP could cause significant decrease in plasma renin activity (PRA), angiotensin II (AII) and aldosterone (Ald). After the administraticn of HPANP, PRA, AII and Ald in the coronary sinus were decreased by 73. 2% (P<0.01), 68. o% (P<0.01) and 73. 6% (P<0.01), and the hormones in peripheral venous blood by 63. 3% (P<0.01), 53. 3% (P<0.01) and 64. 9% (P<0.01), respectively at the dose of 6 μg/kg. While PRA, AII and Ald in the coronary sinus and in peripheral venous blood decreased by 55. 9%, 55. 3%, 61. 9%, and 54. 0%, 42. 3%, 53, 3%, respectively at the 3μg/kg dose level. At the higher dose, HPANP increased left ventricular systolic pressure (LVSP, +13. 1%, P<0. 05), +dP/dtmax(+24.1 %, P<0.01), -dp/dtmax (+35.9%, P<0.01), and VCE(+28.9%, P<0.05). Mean arterial pressure and left ventricular end-diastolic pressure (LVEDP) were decreased (-15.0%, P<0.01, and 29. 6%, P<0.01, respectively). In contrast, the lower dose caused no significant changes of LVSP, +dp/dtmex,dp/dtmax and VCE(not including LVEDP, - 20. 5 %, P<0.05). Neither of the doses caused significant changes in heart rate and T value- Normal saline infusion has no effects on cardiac function and circulating RAAS- We conclude that in ischemic heart failure, intracoronary administration of HPANP can significantly suppress the activity of circulating RAAS, and improve cardiac function by reducing pre- and after-load of the heart, but has no direct myocardial effects.

Serum RAAS molecules and their relationship with the systemic inflammatory response and target organ function in patients with severe acute pancreatitis

Objective:To explore the relationship of renin-angiotensin-aldosterone system (RAAS) activity with the systemic inflammatory response and target organ function in patients with severe acute pancreatitis.Methods: A total of 78 patients with severe acute pancreatitis who were treated in our hospital between August 2012 and March 2016 were selected as the observation group, and 50 healthy people who underwent physical examination in our hospital during the same period were selected as the normal control group. The differences in the contents of RAAS indexes, inflammation indexes as well as liver and kidney function indexes were compared between the two groups, and Pearson test was used to evaluate the correlation between RAAS activity and illness in patients with severe acute pancreatitis. Results: Serum RAAS indexes E, Ang-Ⅱ and ALD levels of observation group were higher than those of normal control group;serum inflammation indexes IL-6, IL-8, IL-10 and CRP levels were higher than those of normal control group;serum liver function indexes ALP,γ-GT and AST levels were higher than those of normal control group;serum kidney function indexes Scr, BUN and UA levels were higher than those of normal control group. The RAAS activity of patients with severe acute pancreatitis was directly correlated with serum levels of inflammation indexes as well as liver and kidney function indexes.Conclusion: The RAAS activity increases in patients with severe acute pancreatitis, and the specific increase extent is consistent with systemic inflammatory response as well as liver and kidney function damage.

Effect of dexmedetomidine combined with ulinastatin on RAAS system,coagulation indexes and oxygen free radicals after acute aortic dissection surgery

Objective: To study the effect of dexmedetomidine combined with ulinastatin on RAAS system, coagulation indexes and oxygen free radicals after acute aortic dissection surgery. Methods: A total of 48 patients with aortic dissection who accepted endovascular graft exclusion treatment in the hospital between May 2014 and February 2017 were selected and randomly divided into two groups, group A received dexmedetomidine, ulinastatin combined with general anesthesia, and group B received general anesthesia. The RAAS hormones, coagulation indexes and oxygen free radical indexes were measured 1 d before surgery, during operation and 24 h after surgery. Results: During operation and after operation, serum REN, AT-II, ALD, FIB, DD, MDA and MPO contents as well as APTT and TT levels of both groups of patients were significantly higher than those before operation while TAOC and TSOD contents were significantly lower than those before operation, and serum REN, AT-II, ALD, FIB, DD, MDA and MPO contents as well as APTT and TT levels of group A were significantly lower than those of group B while TAOC and TSOD contents were significantly higher than those of group B. Conclusion: Dexmedetomidine combined with ulinastatin for acute aortic dissection can inhibit RAAS system and oxygen free radical generation and improve coagulation function.

The correlation between serum MR-proANP and neurohumoral system change in patients with acute myocardial infarction

Objective:To study the correlation between serum midregional pro-atrial natriuretic peptide (MR-proANP) and neurohumoral system change in patients with acute myocardial infarction (AMI).Methods:A total of 56 patients who were diagnosed with acute myocardial infarction in our hospital between May 2013 and December 2015 were selected as the AMI group, 45 patients with stable angina pectoris who were treated during the same period were selected as the SAP group, and 60 healthy volunteers who received physical examination during the same period were selected as the control group. Serum was collected to determine the levels of MR-proANP, neurohumor-related hormones and myocardial remodeling-related molecules. Results:Serum MR-proANP, NE, E, PRA, Ang-II, ALD, MMP2, MMP10, PICP and PIIINP levels of AMI group were significantly higher than those of SAP group and control group;serum NE, E, PRA, Ang-II, ALD, MMP2, MMP10, PICP and PIIINP levels in AMI group of patients with high MR-proANP levels were significantly higher than those in AMI group of patients with low MR-proANP levels.Conclusions:Serum MR-proANP significantly increases in patients with AMI and is closely related to the degree of compensatory neurohumoral change and myocardial remodeling.

The value of serum PCT levels for assessing the inflammatory response and RAS activation degree in patients with severe acute pancreatitis

Objective:To study the value of serum PCT levels for assessing the inflammatory response and RAS activation degree in patients with severe acute pancreatitis.Methods:A total of 76 patients with acute pancreatitis who were treated in our hospital between May 2013 and April 2016 were collected, and 50 patients with pure diarrhea who received infusion treatment in our hospital during the same period were selected as the control group. Serum PCT levels of both groups were detected, and the observation group were further divided into high PCT group and low PCT group (n=38) according to the median of PCT levels. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of pro-inflammatory factors, anti-inflammatory factors and RAS indexes.Results:Serum PCT level of observation group was higher than that of control group;serum pro-inflammatory factors IL-1β, IL-6, CRP and TNF-α levels of high PCT group and low PCT group were higher than those of control group, anti-inflammatory factors IL-4, IL-10 and IL-13 levels were higher than those of control group, and RAS indexes AngⅡ, RA and ALD levels were higher than those of control group;serum pro-inflammatory factors IL-1β, IL-6, CRP and TNF-α levels of high PCT group were higher than those of low PCT group, anti-inflammatory factors IL-4, IL-10 and IL-13 levels were higher than those of low PCT group, and the RAS indexes AngⅡ, RA and ALD levels were higher than those of low PCT group.Conclusion:The serum PCT levels can assess the inflammatory response and RAS activation degree in the patients with severe acute pancreatitis.

Balancing Effect of Biejiajian Oral Liquid(鳖甲煎口服液)on ACE-AngⅡ-AT1R Axis and ACE2-Ang-(1–7)-Mas Axis in Rats with CCl_4-Induced Hepatic Fibrosis

Objective： To explore the effect of Biejiajian Oral Liquid（鳖甲煎口服液, BOL） on CCl4-induced hepatic fibrosis in rats by detecting the changes in the levels of angiotensinⅡ（AngⅡ）, angiotensin-（1–7） [Ang-（1–7）], angiotensin-converting enzyme（ACE）, ACE2, angiotensinⅡ type 1 receptor（AT1 R）, Mas, etc. Methods： A total of 180 Wistar rats were randomly divided into two groups by random digital table method： prevention experiment and treatment experiment. Each group was further subdivided into the fol owing 6 subgroups： normal control group, model group, vitamin E [100 mg/（kg·d）, VE] group, enalapril [10 mg/（kg·g）, Ena] group, high-dosage [20 g/（kg·d）] BOL group, and low-dosage [10 g/（kg·d）] BOL group. The hepatic fibrosis rat model was established by subcutaneous injection of CCl4 for 6 weeks. Prevention experiment and treatment experiment were administered with specific drugs at different times. At the end of treatment experiment, the pathological changes of liver were observed after hematoxylin-eosin staining. The expressions of ingredients in renin-angiotensin-aldosterone system（RAAS） such as AngⅡ, Ang-（1–7）, ACE, ACE2, AT1 R, Mas, renin, CYP11 B2 and angen in liver were detected by enzyme linked immunosorbent assay, immunohistochemistry method or reverse transcription-polymerase chain reaction, respectively. Results： The levels of AngⅡ and Ang-（1–7） at the 6 th week increased by 496.10% and 73.64%, respectively, compared with those at the 2 nd week in the model group（P〈0.01）. With prevention or treatment with high-dosage BOL, there was an evident reduction of AngⅡ level but an improvement of Ang-（1–7） level. Specifically, AngⅡ level of high-dosage group decreased by 77.50% in prevention experiment（P=0.000） and by 76.93% in treatment experiment（P=0.002） compared with that in the model group. Ang-（1–7） level increased by 91.69% in prevention experiment（P=0.006） and by 70.77% in the treatment experiment（P=0.010） compared with that in the model group. The expression levels of m RNA of renin, ACE, CYP11 B2, angen and AT1 R decreased by 58.15%, 99.90%, 99.84%, 99.99% and 99.99%（al P〈0.01）, respectively. Conclusions： BOL could help resist liver fibrosis in rats by enhancing the level of each ingredient in ACE2-Ang-（1–7）-Mas axis, while decreasing the level of each ingredient in ACE-AngⅡ-AT1 R axis. To some extent, BOL could enhance the regulation of RAAS in rats with CCl4-induced hepatic fibrosis.

Protective Effects of Sapindus Saponins in Spontaneously Hypertensive Rats

Objectives： To investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms. Methods： Thirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups （8 in each group）： model group （placebo）, positive control group （27 mg/kg of Captopril Tablets）, Sapindus saponins groups （27 mg/kg and 108 mg/kg, respectively）. Another 8 healthy Wistar-Kyoto strain （WKY） rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter （BP-6）. Furthermore, the contents of angiotensin Ⅱ （Ang Ⅱ） in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay （ELISA）, the gene expression of receptor angiotensin type 1 （AT1R） in aorta was determined by quantitative real- time polymerase chain reaction （qRT-PCR）. The protein expression of transforming growth factor- β1 （TGF- 1β1） and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase （p-p38MAPK） was determined by Western blotting. The contents of interleukin （IL）-1, IL-6 and tumor necrosis factor （TNF） in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin （HE） or Masson staining. Results： Thirty minutes after single or continuous treatment, systolic blood pressure （SBP） was reduced significantly in Sapindus saponins groups. And the contents of Ang 11, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF- β1 were significantly suppressed dose-dependently （P〈0.05 or 1=〈0.01）. With the Sapindus saponins treatment, compared with those of the model group, the cardiac and aortic pathological changes were ameliorated significantly. Conclusions： Our findings suggest that Sapindus saponins might have protective effects in spontaneously hypertensive rats, the cellular and molecular mechanisms of which might be relevant to the regulation of inflammatory responses mediated by p-p38MAPK signal pathway based on activated Ang Ⅱ and AT1R.