The present study was aimed at investigating the molecular regulation of the renin- angiotensin system (RAS) in two-kidney, one clip (2K1C) hypertension. The expression of renin, angiotensinogen and angiotensin II receptor genes was determined by Northern blot analysis in rats made 2K1C hypertensive for 2 or 4 weeks. The expression of renin gene was increased in the clipped kidney and decreased in the contralateral non-clipped kidney at weeks 2 and 4. The expression of angiotensinogen gene was not significantly altered at week 2, but increased at week 4 in the clipped kidney. However, it was not significantly altered in the contralateral kidney either at week 2 or 4. Nor was the expression of angiotensinogen gene significantly altered in the liver either at week 2 or 4. On the other hand, the expression of angiotensin II receptor gene was decreased at week 2, and increased at week 4 in the clipped kidney, whereas it was not significantly changed in the contralateral kidney either at week 2 or 4. In the liver, the expression of angiotensin II receptor gene was not significantly altered at week 2, but decreased at week 4. These results suggest that the components of RAS are transcriptionally regulated in 2K1C hypertension in a manner dependent on tissues and duration of hypertension.
Angiotensin II* ; Angiotensinogen* ; Angiotensins* ; Animals ; Blotting, Northern ; Hand ; Hypertension ; Kidney ; Liver ; Rats* ; Receptors, Angiotensin* ; Renin

Pregnancy-induced hypertension(PIH) is one of the major causes of maternal, fetal and neonatal morbidity and mortality. Although many causes are encountered, etiology of PIH is still unknown. A molecular variant of angiotensinogen, M235T, reported to be linked with essential hypertension and PIH. This study was to evaluate the molecular variation of angiotensinogen in Korean pregnancy-induced hypertension. Our results did not provide any definite relation with the molecular variant of angiotensinase, M235T, and Korean PIH.
Angiotensinogen* ; Female ; Hypertension ; Hypertension, Pregnancy-Induced* ; Mortality ; Polymerase Chain Reaction ; Pregnancy

OBJECTIVES: Previous studies have suggested an association of pregnancy-induced hypertension(PIH) with several genes involved in cardiovascular control. The objectives of this study were to evaluate the association between PIH and angiotensinogen(AGT) M235T gene and also to study the association between PIH and angiotensin-converting- enzyme(ACE). METHODS: DNA was extracted from whole blood, cheek swabs, and blood spot cards of 39 PIH patients and 54 controls. Controls consisted of women who had undergone at least two term pregnancies unaffected by PIH. All samples were genotyped for all the polymorphism using PCR of known alleic variants. Results were ananlyzed with a kappa2 contingency table. RESULTS: Four of 13 women with mild PIH(30.8%) and thirteen of 26 women with severe PIH(50.0%) were heterozygous for AGT M235T mutation compared with 26 of 54 controls(48.1%). Two of 13 women with mild PIH(15.4%) and two of 26 women with severe PIH(7.7%) were homozygous for AGT M235T mutation compared with 10 of 54 controls(18.6%). Six of 7 women with mild PIH(85.7%) and ten of 21 women with severe PIH(47.6%) were ID type for ACE gene compared with 31 of 56 controls(55.4%). One of 7 women with mild PIH(14.3%) and seven of 21 women with severe PIH(33.4%) were DD type for ACE gene compared with 15 of 56 controls(26.7%). There was no significance between mild, severe PIH patients and controls for AGT M235T mutation and ACE gene polymorphism. CONCLUSION: In Korean population, AGT M235T mutation and ACE gene are not associated with an increased risk for PIH.
Angiotensinogen* ; Cheek ; DNA ; Female ; Humans ; Hypertension, Pregnancy-Induced* ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Pregnancy

OBJECTIVETo evaluate the influence of the angiotensinogen(AGT) gene M235T variant on the prevalence and severity of hypertrophic cardiomyopathy(HCM).

METHODSThe authors conducted a case-control study on 152 subjects, including 72 HCM patients and 80 normal controls. Polymerase chain reaction(PCR) combined with restriction fragment length polymorphism(RFLP) was used to detect the M235T variant of AGT gene. Interventricular septum thickness, left ventricular posterior wall thickness and apical wall thickness were measured by means of M-mode echocardiography under two-dimensional guidance in the parasternal long-axis plane and apical two- and four-chamber views.

RESULTS(1) The genotype distributions of AGT gene in both groups were in agreement with Hardy-Weinberg equilibrium. (2) The genotype distributions of the M235T variant differed significantly in HCM patients and controls(chi-square=6.090 P<0.05). The frequencies of TT genotype and T235 allele in HCM patients were higher than did the patients in controls(TT genotype 0.63 vs 0.45 OR=2.037 95%CI 1.064-7.899 P<0.05 T235 allele 0.78 vs 0.64 OR=1.990 95%CI 1.197-3.308 P<0.01). (3)The patients with the TT genotype had significantly greater mean left ventricular maximal wall thickness than did the patients with the MM and MT genotypes [(19.1+/-4.8) mm vs(15.3+/-2.6)mm and(16.2+/-5.1)mm F=4.261 P<0.05].

CONCLUSIONThe variant M235T of the AGT gene is significantly associated with HCM in this population. The genotype TT or allele T might be a genetic risk factor for the development and extent of hypertrophy in HCM patients.

Adult ; Aged ; Angiotensinogen ; genetics ; Cardiomyopathy, Hypertrophic ; genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic

Angiotensinogen ; metabolism ; Animals ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System

OBJECTIVETo evaluate the relationship of six single nucleotide polymorphisms(SNPs) and their haplotypes of angiotensinogen(AGT) gene to essential hypertension(EH) in Chinese Han population.

METHODSThe genotypes in 185 patients with EH and 185 healthy controls were determined by the method of ABI PRISM SNaPshot Multiplex Kit using six AGT gene polymorphisms at position -217(G/A), -152(G/A), -20(A/C) and -6(G/A) in the promoter region and T174M, M235T in exon 2.

RESULTSThe distribution of AGT genotypes and alleles frequencies showed no significant difference between the group of EH and group of controls (P>0.05). However, haplotype analysis revealed that H4 haplotype frequency, which included -152A, -20C, -6A and 235T alleles, was significantly increased in the group of EH (P<0.05).

CONCLUSIONG-152A, A-20C, G-6A and M235T polymorphisms of AGT gene might play an important role in the occurrence of EH in Chinese Han population.

Adult ; Aged ; Angiotensinogen ; blood ; genetics ; Female ; Haplotypes ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

PURPOSE: There were experimental evidences supporting that intrarenal activation of the renin-angiotensin system contributes to increase BP, proteinuria and urinary angiotensinogen (UAGT) excretion. The purpose of this prospective, open label, controlled study was to investigate the effect of losartan on proteinuria and UAGT excretion in chronic non-diabetic proteinuric (0.4 to 2.0 g/day) renal disease with normal renal function (glomerular filtration rate, GFR>60 mL/min/1.73m2). METHODS: Thirty two patients were randomly allocated to the losartan group (100 mg/day; n=17) or the control group (n=15). Systolic BP, diastolic BP, estimated GFR, urinary protein to creatinine ratio (UP/Cr), UAGT and plasma angiotensinogen (PAGT) level were compared between two groups at baseline, 6 months and 12 months. RESULTS: UP/Cr (1.13+/-0.36 g/g vs. 1.07+/-0.34 g/g) was similar in two groups at baseline. Target BP (<140/90 mmHg) was maintained in both groups. After 6 months, UP/Cr (0.63+/-0.35 g/g vs. 0.97+/-0.41 g/g, p<0.01) was significantly decreased in the losartan group compared to the control group. In addition, UAGT (baseline 1.0) was noticeably suppressed in the losartan group (0.72+/-0.42 vs. 1.07+/-0.81, p=0.13). However, PAGT was not changed in both groups. Moreover, our study at 12 months period has demonstrated continuous suppression of UP/Cr (0.79+/-0.53 g/g vs. 1.00+/-0.50 g/g, p=0.06) and UAGT (0.60+/-0.51 vs. 1.51+/-1.36, p<0.05) in the losartan group. UP/Cr was highly correlated with UAGT (Correlation Coefficient=0.74, p<0.01), but not with PAGT. CONCLUSION: Losartan not only induced a remarkable decrease in proteinuria but also contributed a reduction in UAGT in patients with chronic non-diabetic proteinuric renal disease.
Angiotensinogen ; Creatinine ; Filtration ; Humans ; Losartan ; Plasma ; Prospective Studies ; Proteinuria ; Renin-Angiotensin System

The present study was aimed at investigating the effect of cyclosporine A (CsA) on the renal renin-angiotensin systems. In rats chronically treated with CsA, the intrarenal expression of various genes of the renin-angiotensin system was assessed by Northern blot analysis. Along with the increases in plasma and renal renin activities, chronic CsA-treatment differentially affected the renal expression of renin-angiotensin system. The treatment with CsA for one week did not significantly alter the expression of either type 1 angiotensin II receptor (AT1A) or angiotensinogen gene, but increased the renin mRNA level. The three-week-treatment caused increases in the expression not only of renin but also of AT1A and angiotensinogen genes. Supplementation with L-arginine kept the expression of renin mRNA normal in the one-week-treated, but failed to prevent the alterations of the gene expression in the three-week-treated. Feedback control among components of the renin-angiotensin system also influences angiotesinogen. In the liver, the expression of angiotensinogen mRNA was decreased by the CsA-treatment for either one- or three-weeks. In conclusion, chronic CsA-treatment is associated with a differential expression of various genes for the renin-angiotensin system. L-Arginine may be effective in maintaining the normality of renin-angiotensin system only during early period after beginning the use of CsA.
Angiotensinogen ; Animals ; Arginine ; Blotting, Northern ; Cyclosporine* ; Gene Expression ; Liver ; Plasma ; Rats ; Receptors, Angiotensin ; Renin ; Renin-Angiotensin System* ; RNA, Messenger

Urinary angiotensinogen (AGT) is potentially a specific biomarker for the status of the intrarenal renin-angiotensin system (RAS) in patients with diabetes mellitus. We explored whether changes in urinary AGT excretion levels were associated with the deterioration of kidney function in type 2 diabetes patients with preserved kidney function. Urinary baseline AGT levels were measured in 118 type 2 diabetic patients who were not taking RAS blockers and who had estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m². A total of 91 patients were followed-up for 52 months. Changes in urinary levels of AGT (ΔAGT) were calculated by subtracting urinary AGT/creatinine (Cr) at baseline from urinary AGT/Cr after 1 year. ΔAGT was significantly inversely correlated with annual eGFR change (β = −0.29, P = 0.006; β = −0.37, P = 0.001 after adjusting for clinical factors). RAS blockers were prescribed in 36.3% of patients (n = 33) during follow-up. The ΔAGT values were lower in the RAS blockers users than in the non-RAS blockers users, but the differences were not statistically significant (7.37 ± 75.88 vs. 22.55 ± 57.45 μg/g Cr, P = 0.081). The ΔAGT values remained significantly correlated with the annual rate of eGFR change (β = −0.41, P = 0.001) in the patients who did not use RAS blockers, but no such correlation was evident in the patients who did. ΔAGT is inversely correlated with annual changes in eGFR in type 2 diabetes patients with preserved kidney function, particularly in RAS blocker-naïve patients.
Angiotensinogen* ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Diabetic Nephropathies ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Kidney* ; Renin-Angiotensin System

We tested the hypothesis that angiotensin-converting enzyme (ACE) and angiotensinogen gene polymorphism influence the incidence, development and outcome of preeclampsia. Subjects were recruited from 90 Korean patients with preeclampsia during pregnancy and 98 age-matched controls. After isolation of DNA, polymerase chain reactions (PCR) were carried out to detect polymorphism of the ACE and angiotensinogen. M235T and T174M genotypes of angiotensinogen were determined by digestion with restriction enzyme endonuclease Tth 111-I and NCo I, respectively. The frequency of DD genotype was significantly greater in preeclampsia (0.36) than in controls (0.14) (p<0.05). The frequency of D allele was 0.55 in preeclampsia and 0.40 in controls (p<0.05). There were no differences in the onset of preeclampsia and pregnancy outcomes according to the ACE genotypes. There was no difference in the frequency of a allele of angiotensinogen M235T between the groups (0.79:0.78 in preeclampsia : controls). The frequency of T allele of angiotensinogen T174M gene was slightly increased, but not significantly, in preeclampsia (0.11) than in controls (0.07). In a multivariate analysis, only ACE genotype was associated with the development of preeclampsia (beta=0.27, p=0.05). In conclusion, a molecular variant of ACE, but not angiotensinogen, gene is associated with preeclampsia in Korean women.
Adult ; Angiotensinogen/*genetics ; Female ; Gene Frequency ; Genotype ; Human ; Korea ; Peptidyl-Dipeptidase A/*genetics ; *Polymorphism (Genetics) ; Pre-Eclampsia/*genetics ; Pregnancy