Genomics ; Renin-Angiotensin System ; drug effects ; genetics

A 54-year-old woman with diabetes mellitus was hospitalized with generalized edema and weakness. She was also found to have hypertension, hypokalemia and metabolic alkalosis. Detailed examination showed subnormal plasma renin activity and plasma aldosterone concentration. Adrenal CT scanning revealed no adrenal tumor. A successful treatment with amiloride established the diagnosis of Liddle's syndrome for the patient. Liddle's syndrome, a rare hereditary disease usually found in young patients, should be considered in the differential diagnosis of hypertension even in elderly individuals.
Aldosterone/deficiency* ; Aldosterone/blood ; Alkalosis/genetics* ; Case Report ; Female ; Human ; Hypertension/etiology ; Hypokalemia/genetics* ; Middle Age ; Renin/deficiency* ; Renin/blood ; Syndrome

OBJECTIVETo explore the association between angiotensin-converting enzyme (ACE) and the polymorphisms of N5, N10-methylenetetrahydrofolic acid reductase (MTHFR) gene in patients with ischemic stroke (IS).

METHODSTotally 454 patients with IS (IS group) and 334 controls (control group) were recruited in our study. Their I/D polymorphisms of ACE gene and C677T polymorphisms of MTHFR gene were detected by PCR and denaturing high performance liquid chromatography.

RESULTSThe frequencies of DD, ID, II and CC, CT, TT genotype in IS group were 22.5%, 43.4%, 34.1%, and 51.8%, 40.5%, 7.7%, respectively, and were 17.4%, 45.5%, 37.1% and 56.9%, 38.3%, 4.8% in the control group, respectively. DD genotype was associated with large-artery atherosclerosis (LAA), and TT genotype and T allele were associated with LAA and cardioembolism. Synergistic effects were found between TT and DD/ID DD genotypes in the pathogenesis of ischemic stroke.

CONCLUSIONDD, TT genotype and T allele are risk factors of IS, and ACE gene and MTHFR gene have synergistic effects in the pathogenesis of IS.

Brain Ischemia ; complications ; genetics ; Genetic Predisposition to Disease ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Genetic ; Renin ; genetics ; Stroke ; etiology ; genetics

The present study was aimed at investigating the regulation of atrial natriuretic peptide (ANP) system in association with either enhanced or attenuated activity of the renin-angiotensin system (RAS). The cardiac tissue mRNA and peptide levels of ANP were measured in rats with two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertension. Plasma renin concentration was increased in 2K1C hypertension along with increases of renin mRNA and protein contents in the clipped kidney. On the contrary, it was suppressed in DOCA-salt hypertension along with decreases of renin mRNA and protein contents in the remaining kidney. The plasma ANP concentration was similarly increased in both models of hypertension. The cardiac tissue ANP contents were not significantly changed, but the tissue ANP mRNA levels were upregulated in the hypertrophied heart in these two models of hypertension. It is suggested that the cardiac ANP system is transcriptionally enhanced by cardiac hypertrophy associated with hypertension, independent of the systemic RAS.
Animal ; Atrial Natriuretic Factor/metabolism* ; Desoxycorticosterone ; Gene Expression Regulation ; Hypertension/metabolism* ; Hypertension/chemically induced ; Male ; Myocardium/pathology ; Organ Weight ; Peptides ; RNA, Messenger/analysis ; Rats ; Rats, Sprague-Dawley ; Renin/genetics* ; Renin/blood* ; Renin-Angiotensin System/physiology

Hepatitis B, Chronic ; metabolism ; Humans ; Liver Cirrhosis ; metabolism ; RNA, Messenger ; analysis ; Receptor, Angiotensin, Type 1 ; genetics ; Renin ; genetics

Essential hypertension is a multifactorial disease in which genetic and enviromental factors play an important role. These factors differ in each population. As there are no existing data for the Turkish population, we investigated four Renin Angiotensin System (RAS) gene polymorphisms, the angiotensin converting enzyme (ACE), angiotensinogen (AGN) M235T/T174M and angiotensin II type 1 receptor A1166C polymorphism in 109 hypertensive and 86 normotensive Turkish subjects. Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to determine these polymorphism. The frequencies of person that carry ACE D allel (DD+ID) was significantly higher in hypertensive group (99.1%) than controls (80%) (P<0.000). M235T TT genotype was also found significantly higher in hypertensives than control group (20% vs 2.7%; P<0.001). The frequency of AGN 174M allele was higher in the hypertensive group than control subjects (8.76% vs 4.81%). Frequency of ATR1 C allele (AC+CC genotypes) was found higher hypertensives than controls (39.4% vs 25.9%; P = 0.054). Our results suggest that an interaction exists between the RAS genes and hypertension in Turkish population.
Angiotensinogen/*genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension/*genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/*genetics ; Polymorphism, Genetic/*genetics ; Receptor, Angiotensin, Type 1/*genetics ; Renin-Angiotensin System ; Turkey

For studying the expression and distribution of angiotensinogen (AGT), the C-teminus of rat AGT gene was expressed in E.coli. Rabbits were immunized with expressed AGT protein and sera from different rabbits were raised. ELISA showed a high titre (1:25600) of the antiserum. With the antiserum, Western blotting recognized not only the prokaryotic expressed AGT, but also the endogenous AGT protein in liver tissue of both rats and humans. Using this antiserum, immunohistochemistry showed the expression of AGT protein in islet cells of human pancreas as well as in epithelium of human bile duct. These results suggest that the prokaryotic expressed AGT protein is an effective immunogen for the preparation of anti-AGT antiserum. Our present work provides an important tool for study of the pathophysiological role of AGT as well as local renin-angiotensin system.
Angiotensinogen ; genetics ; immunology ; Animals ; Antibodies, Monoclonal ; biosynthesis ; Escherichia coli ; genetics ; metabolism ; Humans ; Immune Sera ; biosynthesis ; immunology ; Immunization ; Rabbits ; Rats ; Recombinant Proteins ; biosynthesis ; genetics ; immunology ; Renin-Angiotensin System ; physiology

OBJECTIVETo study on the association of M235T polymorphism of the angiotensinogen gene extron 2 (AGT/M235T) and essential hypertension (EH) in Chinese population by means of Meta-analysis.

METHODSOdds ratios (OR) of AGT M235T genotype distributions in EH patients against healthy controls were analyzed. All the relevant studies were identified, poor-qualified studies eliminated, and the risk of publication bias excluded. The Meta-analysis software, REVMAN4.1, was applied for investigating heterogeneity among individual studies and summarizing the effects across studies.

RESULTSA total of 853 cases and 835 controls from 10 studies were included. No heterogeneity among the studies was noticed. The frequencies of the AGT TT, MT and MM genotypes were 65%, 30%, and 4.9% in cases and 50.6%, 41.8% and 7.5% in controls respectively. The frequencies of the AGT T allele were 80% in cases and 72% in controls. The pooled OR (with 95% CI) of TT vs MT + MM was 1.76 (1.44 - 2.16) (P < 0.000 01) with T vs M 1.54 (1.31 - 1.81). The pooled OR of MM vs MT + TT was 0.67 (0.45 - 1.00) (P = 0.05).

CONCLUSIONIn Chinese population (mainly the Hans), TT genotype might be associated with the increased risk of EH while MM genotype be associated with low risk of EH.

Alleles ; Angiotensinogen ; genetics ; Blood Pressure ; China ; epidemiology ; Exons ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Odds Ratio ; Polymorphism, Genetic ; Renin-Angiotensin System ; genetics

OBJECTIVETo investigate the effect of tanshinone II(A) on the expression of different components in the renin-angiotensin system of left ventricles of renal hypertensive rats.

METHODThe renal hypertension model was established in rats by the two-kidney-one-clip (2K1C) method. In the experiment, all of the rats were randomly divided into four groups (n = 15 per group) before the operation: the sham-operated (Sham) group, the hypertensive model (Model) group, the low-dose tanshinone II(A) group and the high-dose tanshinone II(A) group. At 5 week after the renal artery narrowing, the third and fourth groups were administered with 35 mg kg(-1) x d(-1) and 70 mg x kg(-1) x d(-1) of tanshinone II(A), respectively. The blood pressure in rats was determined by the standard tail-cuff method in each week after the operation. After the drug treatment for 8 weeks, all the rats were put to death, and their left ventricles were separated to determine the ratio of left ventricle weight to body weight (LVW/BW), the myocardial collagen content, and the expressions of different components in myocardial RAS, including angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), angiotensin 1-type receptor (AT1R), Mas receptor mRNA expression and angiotensin II (Ang II) and angiotensin (1-7) [Ang (1-7)] content.

RESULTCompared with the sham group, the hypertensive model group exhibited a markable increase in the content of Ang II and Ang (1-7) and the mRNA expressions of ACE, ACE2, AT1R and Mas (P < 0.01). However, the treatment with tanshinone II(A) showed the does dependence, inhibited left ventricle hypertrophy, decreased myocardial Ang II content and the mRNA expression of ACE and AT, R in renal hypertensive rats (P < 0. 01) , further increased the myocardial Ang (1-7) content and the mRNA expression of ACE2 and Mas (P < 0.01) , but without any change in the blood pressure of hypertensive rats.

CONCLUSIONThe treatment with tanshinone II(A) could inhibit left ventricle hypertrophy of renal hypertensive rats. Its mechanism may be partially related to the expression of different components in the renin-angiotensin system for regulating myocardial tissues.

Angiotensin I ; genetics ; metabolism ; Angiotensin II ; genetics ; metabolism ; Animals ; Blood Pressure ; drug effects ; Diterpenes, Abietane ; administration & dosage ; Heart Ventricles ; drug effects ; metabolism ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; physiopathology ; Male ; Peptide Fragments ; genetics ; metabolism ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Renin ; genetics ; metabolism ; Renin-Angiotensin System ; drug effects

BACKGROUND/AIMS: There has been controversy about the role of Toll-like receptor 2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact relationship between TLR2 and RAS is not known. The aim of this study was to determine whether the RAS modulates TLR2. METHODS: We used 8-week-old male wild type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral ureteral obstruction (UUO) was induced by complete ligation of the left ureter. Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular and histologic evaluations were performed. RESULTS: Ang II infusion increased mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys (p < 0.05). There were no differences in tissue injury score or mRNA expression of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming growth factor beta (TGF-beta) between TLR2-KO UUO and WT UUO kidneys. However, aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, OPN, and TGF-beta in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys. CONCLUSIONS: TLR2 deletion induced activation of the RAS in UUO kidneys. Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on UUO injury of the kidney.
Amides/*pharmacology ; Angiotensin II/pharmacology ; Animals ; Disease Models, Animal ; Fibrosis ; Fumarates/*pharmacology ; Kidney/*drug effects/metabolism/pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Nephritis, Interstitial/genetics/metabolism/pathology/*prevention & control ; RNA, Messenger/genetics/metabolism ; Renin/*antagonists & inhibitors/metabolism ; Renin-Angiotensin System/*drug effects ; Toll-Like Receptor 2/deficiency/drug effects/genetics/*metabolism ; Ureteral Obstruction/*drug therapy/genetics/metabolism/pathology