Preliminary study on the ability of 68Ga-Pentixafor PET/CT to differentiate between adrenal aldosterone-producing adenoma and nonfunctional adenoma / 中华内科杂志

Objective:To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods:This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUV max) of the focus on APA and NFA. The related factors of SUV max, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results:68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUV max differentiating APA and NFA was 0.932 ( P<0.001). When the SUV max cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUV max correlated positively with lesion size ( r=0.598) and aldosterone/renin activity ratio ( r=0.313) and correlated negatively with potassium level ( r=-0.286), renin activity ( r=-0.240) and age of diagnosis ( r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions:68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUV max of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

Advances in Medical Treatment of Primary Aldosteronism / 中国医学科学杂志(英文版)

Primary aldosteronism (PA) is the most common form of secondary hypertension, with its main manifestations including hypertension and hypokalemia. Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction. The past decade has witnessed the rapid advances in the genetics of PA, which has shed new light on PA treatment. While surgery is the first choice for unilateral diseases, bilateral lesions can be treated with mineralocorticoid receptor antagonists (MRAs). The next-generation non-steroidal MRAs are under investigations. New medications including calcium channel blockers, macrophage antibiotics, and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.

Interpretation on the international consensus of the pathological diagnosis of unilateral primary aldosteronism / 中华内分泌代谢杂志

Unilateral primary aldosteronism (UPA) is a common form of PA that is surgically curable by adrenalectomy of the overactive gland. Pathological evaluation of resected adrenals is crucial in the diagnosis of UPA, and its subsequent treatment and follow-up as well. Histomorphological evaluation is the basis for the pathological diagnosis of UPA, and the wide use of aldosterone synthase immunohistochemical staining in recent years has greatly improved the pathological diagnosis of UPA. However, there is a lack of standardized nomenclature and diagnostic criteria. Therefore, consensus on the histopathologic diagnosis of UPA were developed by an international group of pathologists led by Tracy Ann Williams, and published in J Clin Endocrinol Metab, 2021. This article will elaborates on the key points in the consensus to advance the understanding and overall improve clinical mangement of UPA.

Association between the polymorphism of aldosterone synthase gene promoter-344T/C and preeclampsia in Qinghai Province / 解剖学报

Objective To investigate the relationship between preeclampsia (PE) and polymorphism of aldosterone synthase gene (CYP11B2) promoter region-344T/C in Qinghai Province. Methods A total of 120 PE subjects and 155 normal pregnancy subjects were studied. The genotype of CYP11B2 was analyzed by polymerase chain reaction fragment length polymorphism (PCR-RFLP). The mutation was confirmed by sequencing. Results The frequencies of CYP11B2 TT, CT and CC genotype in the PE group were 43.0%, 45.6%, and 11.4%, and in the control group were 51.0%, 45.1%, and 3.9%, respectively. There was difference in frequency distribution of CYP11B2 genotype between the PE and control groups. The frequency of C allele in the PE group was higher than the control group (χ

Association of polymorphisms of CYP11B2 gene –344C/T and ACE gene I/D with antihypertensive response to angiotensin receptor blockers in Chinese with hypertension

The aim of this study was to determine whether the polymorphism of aldosterone synthase (CYP11B2) –344C/T and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) were associated with the response of blood pressure (BP) to telmisartan treatment. After a two-week single-blind placebo run-in period, 148 patients with mild-to-moderate primary hypertension received monotherapy of telmisartan with 80 mg/day and then were followed up for eight weeks. Polymorphisms of CYP11B2 –344C/T and ACE I/D gene were determined through polymerase chain reaction-restriction fragment polymorphism analysis. The relationship between these polymorphisms and changes in BP was monitored and evaluated after eight weeks of treatment. With respect tothe polymorphism of CYP11B2 –344C/T, the reduction in diastolic BP was significantly greater in patients carrying the C allele (CC+CT) compared with those carrying the TT genotype. There was no significant differences between ACE I/D polymorphism and BP reduction after treatment. We concluded that the aldosterone synthase –344C/T polymorphism was related to the antihypertensive treatment with telmisartan in hypertensive patients.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Meta analysis of the association between CYP11 B2 gene polymorphism and left ventricle hypertrophy / 中华胸心血管外科杂志

Objective To investigate the association between CYP11 B2 gene polymo-rphism and left ventricle hypertrophy with meta analysis.Methods Literatures about the association of CYP11 B2 gene polymorphism and left ventricle hypertrophy from January 1992 to December 2011 were searched.The electronic databases retrieved from Pubmed,Embase,China national knowledge intemet,Chinese biological medicine disk,VIP fulltext database and Wanfang fulltext database.Odds ratio of CYP11 B2 genotype distributions in left ventricle hypertrophy patients comparing with healthy control were analyzed.RevMan5.1 software was applied for investigating hereogeneity among individual studies and summarizing effects with proper statistical methods.Six case control studies were enrolled.Results A total of 541 cases and 553 controls were enrolled for the study.The pooled OR of CC vs TT + TC genotype was 1.15 (95％ CI:0.74 ～ 1.80) (Z =0.63,P =0.53) in the subgroup of hypertension,and the pooled OR of CC vs TT + TC genotype was 1.15 (95 ％ CI:0.74 ～ 1.80) (Z =0.63,P =0.53) in the subgroup of race.The pooled OR of C vs T allele was 1.15 (95％ CI:0.76 ～ 1.74) vs 0.87 (95％ CI:0.58 ～ 1.31) (Z =0.67,P =O.50).Conclusion Whether the hypertension or the race,the genotype of CYP11 B2 polymorphism has no association with an increased risk of left ventricle hypertrophy.

Genetic aspects in primary aldosteronism / 中华内分泌代谢杂志

Primary aldosteronism (PA) is one of the common forms of secondary hypertension.Compared with essential hypertension patients,PA patients have a higher incidence of target organ damage and cardiovascular events.Elucidation of the underlying molecular mechanisms will likely aid the development of targeted treatments and improve prognosis for PA patients.At present,studies have elucidated the pathogenesis of familial hyperaldosteronism type Ⅰ,while the study of the pathogenesis of other subtypes is still in progressing.This review introduces the current studies on the molecular genetics of primary aldosteronism.

Aldosterone Synthase Deficiency Type II with Hypospadias.

Aldosterone synthase deficiency (ASD) type II was diagnosed in a 3 week old boy with severe dehydration. Elevated plasma renin activity, low-normal aldosterone, increased levels for 18- OH corticosterone (18-OHB) and 18-OH-deoxycorticosterone were measured. Sequencing revealed a homozygous mutation for c554C>T in exon 3 (p.T185I) (CYP11B2). Hypospadias has so far not been reported in ASD.

Recent progress in the treatment of idiopathic aldosteronism / 中华内分泌代谢杂志

The bilateral idiopathic aldosteronism (IHA) is the most common subtype of aldosteronism.Spironolactone is the primary preferred agent due to the pathophysiology of IHA and the long-standing clinical experience over years.If patients faced with severe side effects of spironolactone or poorly controlled blood pressure by this first-line treatment,additional treatment alternative to spironolactone,second antihypertensive,as well as adrenalectomy are suggested.In recent years,several new agents were developed to treat IHA,such as aldosterone synthase inhibitor and eplerenone.This review introduces these new kinds of medicine in the treatment of IHA.

Correlation between renin-angiotensin-aldosterone system gene polymorphisms and large artery atherosclerotic stroke: a study in a southem Chinese Han population / 国际脑血管病杂志

Objective To study the correlation between the renin-angiotensin-aldosterone system angiotensinogen (AGT) gene M235T,angiotensin Ⅱ type 1 receptor (AGTR1) gene Al166C,aldosterone synthase (CYP11B2) gene -344C/T polymorphisms and large-artery atherosclerotic (LAA) stroke in a southern Chinese Han population.Methods Polymerase chain reaction and gene sequencing technology were used for the genotyping in patients with LAA and normal controls with AGT gene M235T,AGTR1 gene A1166C,and CYP11B2 gene - 344C/T polymorphisms in a southern Chinese Han population,and to determine the correlation between the 3 gene polymorphisms and LAA by binary logistic regression analysis.Results A total of 107 patients with LAA and 142 healthy controls were included in the study.The frequencies of the AGT gene 253TT genotype (66.36％ vs.50.70％,x2 =6.122,P =0.047) and T allele (79.44％ vs.70.07％ ％,x2 =5.581,P =0.018) in the LAA group were significantly higher than those in the control group.The frequencies of the AGTR1 gene 1166CC genotype (0％ vs.0％,x2 =1.494,P =0.222) and C allele (7.48％ vs.4.93％,x2 =1.399,P =0.237) in the LAA group were no significantly differences with those in the control group.The frequencies of the CYP11B2 gene - 344CC genotype (9.35％ vs.4.23％,x2 =3.603,P =0.165) and C allele (27.10％ vs.26.06％,x2 =0.069,P =0.793) in the LAA group were no significant differences with those in the control group.Binary logistic regression analysis showed that there was no significant correlation between the three gene polymorphisms and the simple LAA diseases.The frequencies of AGT gene 235TT genotype (68.00％ vs.41.90％,x2 =12.446,P =0.002) and T allele (79.33％ vs.64.76％,x2 =8.993,P =0.003) in the LAA patients complicated with hypertension were significantly higher than those in the normotensive control group.Logistic regression analysis showed that the odds ratio (OR) exposed to TT genotype was 2.153 (95％ confidence interval [CI] 0.789-5.872).The OR of T allele was 2.089 (95％ CI 1.285-3.396).Conclusions The AGT gene M235T polymorphism is not associated with the simple LAA in the southern Chinese Han population,but it may be associated with the risk of LAA complicated with hypertension;CYP11B2 gene -344C/T polymorphism and AGTR1 gene A1166C polymorphism are not associated with the onset of LAA in the southern Chinese Han population.

Genetic Analyses of the Chimeric CYP11B1/CYP11B2 Gene in a Korean Family with Glucocorticoid-Remediable Aldosteronism

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inheritable form of hyperaldosteronism with early onset hypertension. GRA is caused by unequal crossing-over of the steroid 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the adrenal zona fasciculata under the control of adrenocorticotropin. Here, we describe three cases of GRA in a Korean family. The proband-a 21-yr-old female-was incidentally found to have high blood pressure (170/108 mmHg). Her 46-yr-old father had been treated twice for cerebral hemorrhage at the ages of 29 and 39 yr. Her 15-yr-old brother had a 2-yr history of hypertension; however, he was never treated. Their laboratory test results showed normokalemia, hyporeninemia, hyperaldosteronism, and a high plasma aldosterone concentration-to-plasma renin activity ratio. Normal saline loading failed to suppress aldosterone secretion. However, dexamethasone administration effectively suppressed their plasma aldosterone concentrations. Following genetic analyses with PCR and direct sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located between intron 2 of CYP11B1 and exon 3 of CYP11B2.

Decreased expression of Na,K-ATPase in the kidneys of rats with two-kidney, one-clip hypertension / 대한내과학회지

BACKGROUND/AIMS: This study investigated the role of Na,K-ATPase, the local renin-angiotensin-aldosterone system (RAAS), and atrial natriuretic peptide (ANP) system in the pathogenesis of renal tubular dysfunction and hypertension in rats with two-kidney, one-clip (2K1C) hypertension. METHODS: Adult male Sprague-Dawley rats were made 2K1C hypertensive for 4 weeks. The renal expression of Na,K-ATPase was determined by immunoblotting. The mRNA expression of renin, angiotensin-converting enzyme (ACE), aldosterone synthase (CYP11B2), mineralocorticoid receptor (MR), and the ANP system were determined in the kidney using real-time polymerase chain reaction. RESULTS: The blood pressure was increased in the 2K1C rats, compared with controls. The plasma renin activity and serum aldosterone concentrations were increased, as were the urine output and fractional excretion of sodium. The expression of Na,K-ATPase protein was decreased in the clipped kidney, as compared with the control kidney, while it remained unchanged in the contralateral kidney. The mRNA expression of renin, ACE1, CYP11B2, and MR was increased in the clipped kidney, but unchanged in the non-clipped kidney. The mRNA expression of ACE2 did not differ between the groups. The expression of ANP mRNA was increased in both clipped and non-clipped kidneys, as compared with control kidneys. CONCLUSIONS: The enhanced activity of the local RAAS may result in to ischemic tubular injury and the development of hypertension in 2K1C rats. The downregulation of Na,K-ATPase associated with tubular injury in the clipped kidney may account for the impaired tubular sodium reabsorption in 2K1C hypertension.

Polymorphism of angiotension Ⅱ type 1 receptor gene, angiotensin converting enzyme gene and aldosterone synthase gene and hypertensive disorder complicating pregnancy / 中国综合临床

Objective To explore the relationship among genetic polymorphism of angiotension Ⅱ type 1 re-ceptor(AT1 R) A1166-C, angiotensin converting enzyme (ACE) insertion/deletion (I/D), aldosterone synthase (CYP11B2)-344T/C and hypertensive disorder complicating pregnancy.Methods Polymerase chain reaction-re-striction fragment length polymorphism (PCR-RFLP) assay was used to detect the genotypes of AT1 R A1166-C ,ACE (I/O) ,CYP11B2 -344T/C in 86 cases of hypertensive disorder complicating pregnancy and 175 cases of normal control.Results There was 18 combined types in hypertensive disorder complicating pregnancy cases and normal control cases.Compared to AT1R-AA + ACE-Ⅱ + CYP11B2-TT, Odds ratios (OR) of AT1R-AA + ACE-DO +CYP11B2-TC,AT1 R-AC + ACE-ID+CYP11B2-TC and AT1R-AC+ACE-DD+CYP11B2-TC are 7.289,5.315 and 5.694 respectively.There was no statistical significance among the others.Conclusion In all 18 kinds of combined types, AT1 R-AA + ACE-DO + CYP11B2-TC,AT1R-AC+ACE-ID+CYP11B2-TC and AT1 R-AC + ACE-DD +CYP11B2-TC might increase the susceptibility of hypertensive disorder complicating pregnancy.It is possible that multigenes are interacted in the etiology of hypertensive disorder complicating pregnancy.

Association of polymorphisms in aldosterone synthase and 11 beta-hydroxylase genes with the risk of primary aldosteronism / 中华泌尿外科杂志

Objective To determine the association of mutations in aldosterone synthase (CYPllB2)and 11 beta-hydroxylase(CYP11B1)genes with primary aldosteronism(PA).Methods Five mutations of CYP11B2 and CYP11B1 genes were analyzed in patients with PA and normal population.Among them,intron 2 was detected by 2 independent PCR reactions,and the others were analyzed using Taqman probes.The Haploview 4.0,SNPassoc 1.5-3 and Haplo.stats 1.3.8 were used to analyse the association between polymorphisms and PA.Results All the selected mutations were successfully genetyped.Only rs64lO allelic frequencies in patients with aldosterone-producing adenoma (APA)and idiopathic hyperaldosteronism(IHA)were significantly different with those in controls (P＜0.05).There was a relative excess of AA homozygotes and AG heterozygotes of rs6410 allele in APA group compared with control group(P＜0.01).There were significantly different genotypes AA and AG of rs6410 allele between patients with IHA and controls only after adjusted for age,gender,eeptible haplotype AAAWT was identified to be significantly associated with APA(OR=1.44,95%CI 1.19-1.76).Three susceptible haplotypes AAAWT,AGGWT and AGAWC were identified to be significantly associated with IHA(OR=1.55,95%CI 1.23-1.96;OR=1.49,95%CI 1.17-1.89;OR=1.40,95%CI 1.04-1.88).In contrast,1 protective haplotype GGAWT showed significant difference between patients with APA and controls(OR=0.73,95%CI 0.55-0.97).Conclusion There is a significant association between genetic variations in CYP11B2 and CYP11B1 genes and genetie predisposition to PA.

Aldosterone Synthase Gene (CYP11B2) Polymorphism in Korean End-Stage Renal Disease Patients on Hemodialysis

Aldosterone synthase gene (CYP11B2) -344C/T polymorphism has been reported to be associated with serum aldosterone level, urinary aldosterone excretion, blood pressure, and left ventricular size and mass. The aim of this study was to evaluate the relation between CYP11B2 polymorphism and end-stage renal disease (ESRD) in the Korean population and the association with CYP11B2 polymorphism and cardiovascular morbidity in ESRD patients on hemodialysis. Genotyping was performed in 134 control subjects and 271 ESRD patients for CYP11B2 polymorphism using polymerase chain reaction through subsequent cleavage with restriction enzyme. Also current blood pressure, demographic, anthropometric and biochemical variables were investigated. The genotype distribution did not differ between ESRD patients and controls and there were no significant differences in blood pressure, use of antihypertensive medication, left ventricular hypertrophy and cardiovascular disease among the three genotypes in ESRD patients on hemodialysis. Our findings do not support the hypothesis that CYP11B2 polymorphism may be associated with prevalence of ESRD and suggest that CYP11B2 polymorphism may not be a genetic marker for cardiovascular morbidity in Korean ESRD patients.

Relationship of gene polymorphisms of angiotensin convertion enzyme, aldosterone synthase and α-adducin with subclinical renal lesion / 中华老年医学杂志

Objective To investigate the relationship of gene polymorphisms of angiotensin eonvertion enzyme (ACE), aldosterone synthase (CYP11B2)and α-adducin with subclinical renal lesion. Methods I/D polymorphism of ACE gene, -344T/C polymorphism of CYP11B2 gene and 460G/T polymorphism of α-adduein gene were detected by polymerase chain reaction (PCR) and restrictive fragment length polymorphism(RFLP) in 604 normotensive subjects and 1081 primary hypertensive patients whose creatinine (Cr) were less than 2mg/L. The primary hypertensive and normotensive subjects were divided respectively into normal group (Ccr≥60ml/min) and subclinical renal lesion (Ccr＜60 ml/min) group, according to creatinine clearance rate (Ccr) calculated by Cockcroft-Gault equation. Results ANOVA, contingency X2 and partition of chi-square were selected. The frequencies of different genotypes of ACE, CYP11B2, and α-adducin were in agreement with Hardy-Weinberg equilibrium in our study. Normal renal function group (A group, n=512) and subclinical renal lesion group (B group, n=92) in normotensive subjects, and normal renal function group (C group, n=828) and subclinical renal lesion group (D group, n=252) in hypertensive patients were compared. The patients in B and D groups were older than those in A and C groups (P<0.01). But there were no significant differences in the age between B and D groups, and between A and C groups. The frequency of ACE-DD genotype in D group was the highest (22.6%) among four groups and the frequency of α-adducin-TT genotype in A group was the lowest (13.3%) among four groups (all P<0.01). The differences of genotype frequencies of ACE and α-adducin genes among other three groups were not significant. No significant difference was found in frequencies of genotypes of CYP11B2 among four groups. Conclusions Subclinical renal lesion is increased with the aging. ACE-DD genotype is related with hypertension and subclinical renal lesion, while α-adducin-TT genotype is related with hypertension and subclinical renal lesion. Association between the genotypes of CYP11B2 and subclinical renal lesion is not found.

Increased Expression of Endothelin-1 and CYP11B2 in Gentamicin-Induced Nephropathy in Rat Kidney / 대한신장학회지

PURPOSE: An altered activity of vasoactive hormones as well as aldosterone synthase (CYP11B2) in the kidney may involve the pathogenesis of gentamicin-induced nephropathy. The present study was designed to investigate whether there are changes of local renin-angiotensin-aldosterone system (RAAS) and endothelin (ET) in the kidney of gentamicin-induced nephropathy in rats. METHODS: Male Sprague-Dawley rats (180-200 g) were intramuscularly injected with gentamicin (100 mg/kg per day) for 5 days. Vehicle was given for the control rats. The mRNA expression of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET system and transforming grow factor-beta1 (TGF-beta1) was determined in the kidney by real-time polymerase chain reaction. The protein expression of TGF-beta in the kidney was determined by immunoblotting and immunohistochemistry. RESULTS: Following the gentamicin treatment, a renal failure was noted as evidenced by increased serum concentrations of creatinine along with a decrease of its clearance. TGF-beta1 expression was significantly increased in the kidney in gentamicin treated rats compared with that in controls. The abundance of ET-1 mRNA was significantly increased. The endothelin type A receptor expression was decreased while endothelin type B receptor was not changed. The expression of angiotensin converting enzyme 1 (ACE1) and ACE2 was decreased, whereas renin expression was not changed. The CYP11B2 expression was significantly increased in gentamicin treated rats, while mineralocorticoid receptor expression was not changed. CONCLUSION: The expression of ET-1 and CYP11B2 was up-regulated which may play a role in the pathogenesis of gentamicin-induced nephropathy.

Distribution of aldosterone synthase gene polymorphism in Hebei province in China / 国际检验医学杂志

0.05).(2)Distribution of CYP11B2 -344C/T genotype and allele frequencies in Hebei was significantly different from that of other countries(P

Upregulation of Renin-angiotensin, Endothelin and C-type Natriuretic Peptide in Rat Glomerulus with Bilateral Ureteral Obstruction

The present study was designed to investigate the effects renin-angiotensin-aldosterone system (RAAS), endothelin (ET) and local natriuretic peptide (NP) system for glomerulopathy induced in the experimental bilateral ureteral obstructive rats. Sprague-Dawley male rats (200~220 g body weight) were bilaterally obstructed by ligation of the proximal ureters for 24 hours. Control rats were treated in the same ways, except that no ligature was made. The glomeruli were isolated from cortex by graded sieve methods, and the mRNA expressions of local renin-angiotensin system (RAS), aldosterone synthase (CYP11B2), endothelin-1 (ET-1) and NP system were determined by real-time polymerase chain reaction. Following the bilateral ureteral obstruction, the mRNA expressions of renin, angiotensin converting enzyme 1 as well as ET-1 were increased, while that of angiotensin converting enzyme 2 was not changed. The expressions of CYP11B2 and angiotensin II receptors were not changed. C-type natriuretic peptide (CNP) expression was increased, while its receptors (natriuretic peptide receptor-B) were not changed. We suggest that the upregulation of local RAS and ET play a role in the progressive glomerular injury, and that the enhanced CNP activity also plays a compensatory role in obstructive uropathy in the glomerulus.