No abstract available.
Aldosterone/physiology* ; Animal ; Epithelial Cells/physiology* ; Estradiol/physiology* ; Signal Transduction/physiology*

OBJECTIVETo report the clinical characteristics, biochemical profiles, diagnosis and treatment of one Chinese pedigree with glucocorticoid-remediable aldosteronism (GRA) and to study its molecular mechanism.

METHODSPlasma and urinary aldosterone, cortisol and plasma renin activities were dynamically tested and diagnostic therapy with dexamethasone was undergone in 3 affected subjects. Long-distance PCR as well as DNA sequencing were applied to detect the fusion gene in this pedigree.

RESULTSIn this GRA pedigree, there were 4 affected subjects who had hypertension, hypokalemia and low basic and provoked renin activity. Three patients were given dexamethasone treatment, and had a significant decrease in plasma aldosterone concentrations (PACs) (from 192 +/- 9 ng/L to 87 +/- 7ng/L, P < 0.05) after 5 days. Among them, one patient (II -3) responded quite satisfactorily to the therapy, with serum K(+) rising from baseline value of 2.5 to 2.9, 3.8 and 4.15 mEq/L on the 10th, 28th and 35th days after treatment respectively. Three weeks later, his blood pressure decreased from its original level of 146.3 +/- 1 0.7/94.6 +/- 5.3 mm Hg to 138.3 +/- 3.1/87.3 +/- 6.1 mm Hg (P < 0.05). The other 2 members (III -2 and III -4) showed modest improvement although their PACs decreased significantly. Using long-distance PCR, we found a 3.9 kb band in all 4 affected individuals, which was absent in 5 unaffected members from this pedigree or 8 patients with aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). By DNA sequence analysis, we found that the breakpoint of "unequal crossing-over" is both within intron 2 of the 11beta-hydroxylase gene (CYP11B1) and the aldosterone synthase gene (CYP11B2).

CONCLUSIONSThe excess of mineralocorticoid in patients with GRA can be inhibited by exogenous glucocorticoids. The fusion gene resulting from unequal crossing-over between the 11beta-hydroxylase gene and the aldosterone synthase gene is the pathogenesis of this Chinese GRA pedigree.

Adrenocorticotropic Hormone ; physiology ; Adult ; Aldosterone ; blood ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Hyperaldosteronism ; blood ; drug therapy ; genetics ; Mutation ; Pedigree

BACKGROUNDHypertension often persists after adrenalectomy for primary aldosteronism (PA). Many studies have analyzed the outcomes of adrenalectomy for aldosterone-producing adenomas (APA) to identify predictive factors for persistent hypertension. However, differentially expressed genes in persistent postoperative hypertension remain unknown. Our aim was to describe gene expression profile of persistent postoperative hypertension patients with APA.

METHODSIn this study, we described and compared gene expression profiles in persistent postoperative hypertension and postoperative normotension in Chinese patients with APA using microarray analysis. Confirmation was performed with quantitative real time-polymerase chain reaction analysis. Bioinformatic analysis (gene ontology analysis, pathway analysis and network analysis) was used for further research.

RESULTSMicroarray analysis identified a total of 99 differentially expressed genes, including 18 up-regulated and 81 down-regulated genes. Among the dysregulated genes were fat atypical cadherin 1 as well as fatty acid binding protein 4 and other genes that have not been previously studied in persistent postoperative hypertension with APA. Bioinformatics analysis indicated that differentially expressed genes were associated with lipid metabolic process, metal ion binding, and cell differentiation. Pathway analysis determined that five pathways corresponded to the dysregulated transcripts. The mRNAs-ncRNAs co-expression network was composed of 49 network nodes and 72 connections between 18 coding genes and 31 noncoding genes.

CONCLUSIONSThis study revealed differentially expressed genes in persistent postoperative hypertension with APA and provided a resource of candidate genes for exploration of possible drug targets and prognostic markers.

Adenoma ; metabolism ; physiopathology ; surgery ; Adrenalectomy ; Aldosterone ; metabolism ; Blood Pressure ; physiology ; Gene Expression Profiling ; methods ; Humans ; Hyperaldosteronism ; metabolism ; physiopathology ; surgery ; Postoperative Complications ; Retrospective Studies

OBJECTIVETo investigate the mechanisms of Aldosterone stimulating hepatic stellate cells(HSCs) contraction via Ca2+-independent pathways.

METHODSHSC-T6 cell line was pre-disposed with Aldo 10mumol/L. The cell contraction was detected by silicone-rubber-membrane cultivation directly. The concentration variation of intracellular free calcium in rat HSC was observed by laser confocal microscopy. Besides, HSC-T6 cell line was under pre-disposal treatment with the blocking agents of Aldo receptor -antisterone, protein kinase C (PKC) special blocking agent-Stauro, Rho kinase blocking agent-Y27632 and MLCK special blocking agent-ML-7 respectively prior to stimulation with aldosterone. RT-PCR was used to detect the expression of Rock2, RhoAGTP and RhoGEF in Ca2+- independent pathways mediated by Rho-kinase.

RESULTSAldo could induce HSCs contraction. The concentration of intracellular free calcium in rat HSCs had no change after pre-disposal treatment with Aldo. The mRNA expressions of Rock2, RhoAGTP and RhoGEF increased significantly after treatment with Aldo (0.770+/-0.049, 0.960+/-0.096, 0.180+/-0.006, P is less than 0.01).When inhibited with antisterone, the mRNA expressions of the three elements were (0.440+/-0.166, 0.370+/-0.180 and 0.050+/-0.001, P is less than 0.01), lower than that of Aldo group, but higher in ML-7+Stauro + Aldo groups (0.940+/-0.066, 1.330+/-0.192 and 0.160+/-0.007, P is less than 0.05) as compared to the control group (0.140+/-0.023, 0.540+/-0.111 and 0.110+/-0.012). In the Y27632 + ML-7 + Stauro+Aldo group, the mRNA expression of RhoGEF (0.290+/-0.004, P is less than 0.01)was higher than that of the ML-7 + Stauro + Aldo group (0.160+/-0.007).

CONCLUSIONAldo could induce HSCs contraction via Ca2+-independent pathways and Rho-Rock pathway involved in the process.

Aldosterone ; pharmacology ; Animals ; Cell Line ; Hepatic Stellate Cells ; drug effects ; metabolism ; physiology ; Rats ; Signal Transduction ; drug effects ; rho-Associated Kinases ; metabolism

OBJECTIVETo investigate the acute effects of aldosterone (ALD) on mesenteric resistance vessels in normal or heart failure (HF) rats and its mechanism.

METHODSHF model was adopted by in vivo ligation of left anterior descending coronary artery in SD rats; segments of third-order branches of mesenteric artery were isolated and dissected into about 2 mm rings for isometric force recording.

RESULTSPretreated with ALD for 10 min,phenylephrine (PE)-induced contraction of normal mesenteric artery decreased first and then increased compared to control group along with the increase of the concentration of PE while decreased in HF rats. This effect was attenuated by ALD receptor-special antagonist eplerenone partially. ALD increased Ach-induced endothelial-dependent vascular relaxation significantly compared to control group both in normal and HF rats. Pretreated with ALD and dexamethasone (DEX) for 10 min, the effects of ALD on PE-induced contraction were weakened in mesenteric artery both of normal and HF rats. And this reaction of DEX to ALD-treated mesenteric in normal rats was attenuated by RU486 partially.

CONCLUSIONALD has biphasic effect in PE-induced response on mesenteric artery of normal rats, while reduces the sensitivity of mesenteric artery to PE in HF rats. DEX attenuates the biphasic effect of ALD on artery of normal rat partially but has no significant effect on that of HF rats.

Aldosterone ; pharmacology ; Animals ; Heart Failure ; physiopathology ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Phenylephrine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects

BACKGROUND/AIMS: JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines. METHODS: Cell proliferation was determined by a cell-counting-kit-based colorimetric assay, and vaccinia virus quantitation was performed by quantitative polymerase chain reaction (qPCR) and a viral plaque assay. Also, the intracellular pH was measured using a pH-sensitive dye. RESULTS: Simultaneous treatment with JX-594 and aldosterone significantly increased viral replication in A2780, PC-3, and HepG2 cell lines, but not in U2OS cell lines. Furthermore, the aldosterone treatment time altered the JX-594 replication according to the cell line. The JX-594 replication peaked after 48 and 24 hours of treatment in PC-3 and HepG2 cells, respectively. qPCR showed that JX-594 entry across the plasma membrane was increased, however, the changes are not significant by the treatment. This was inhibited by treatment with spironolactone (an aldosterone-receptor inhibitor). JX-594 entry was significantly decreased by treatment with EIPA [5-(N-ethyl-N-isopropyl)amiloride; a Na+/H+-exchange inhibitor], but aldosterone significantly restored JX-594 entry even in the presence of EIPA. Intracellular alkalization was observed after aldosterone treatment but was acidified by EIPA treatment. CONCLUSIONS: Aldosterone stimulates JX-594 amplification via increased virus entry by affecting the H+ gradient.
Aldosterone/*pharmacology ; Aldosterone Antagonists/pharmacology ; Amiloride/analogs & derivatives/pharmacology ; Animals ; Carcinoma, Hepatocellular/blood/virology ; Cell Line, Tumor ; Humans ; Hydrocortisone/blood ; Hydrogen-Ion Concentration ; Liver Neoplasms/blood/virology ; Neuroprotective Agents/pharmacology ; Oncolytic Virotherapy ; Rabbits ; Spironolactone/pharmacology ; Vaccinia virus/*drug effects/genetics/metabolism/*physiology ; Virus Replication/*drug effects

The effect of aldosterone on connective tissue growth factor (CTGF) was examined in rat embryonic ventricular myocytes. Upon aldosterone treatment, CTGF expression was significantly increased in a dose and time-dependent manner. To explore the molecular mechanism for this upregulation, we examined the role of mineralocorticoid receptor. Pre-treatment of an antagonist (spironolactone) at 5-fold excess of aldosterone blocked the CTGF induction by aldosterone, suggesting that the upregulation was mediated by mineralocorticoid receptor. Aldosterone treatment resulted in activation of ERK1/2, p38 MAPK, and JNK pathways with a more transient pat-tern in p38 MAPK. Blocking studies using pre-treatment of the inhibitor of each path-way revealed that p38 MAPK cascade may be important for aldosterone-mediated CTGF upregulation as evidenced by the blocking of CTGF induction by SB203580 (p38 MAPK inhibitor), but not by PD098059 (ERK1/2 inhibitor) and JNK inhibitor I. Interestingly, JNK inhibitor I and PD098059 decreased the basal level of CTGF expression. On the other hand, pre-treatment of spironolactone abrogated the p38 MAPK activation, indicating that mineralocorticoid receptor mechanism is linked to p38 MAPK pathway. Taken together, our findings suggest that aldosterone induces CTGF expression via both p38 MAPK cascade and mineralocorticoid receptor and that cross-talk exists between the two pathways.
Aldosterone/*pharmacology ; Animals ; Cells, Cultured ; Dose-Response Relationship, Drug ; Gene Expression Regulation/drug effects/physiology ; Heart Ventricles/drug effects/embryology/metabolism ; Immediate-Early Proteins/*metabolism ; Intercellular Signaling Peptides and Proteins/*metabolism ; Myocytes, Cardiac/*drug effects/*metabolism ; Rats ; Receptors, Mineralocorticoid/*metabolism ; Research Support, Non-U.S. Gov't ; Signal Transduction/drug effects/physiology ; Spironolactone/pharmacology ; Up-Regulation/drug effects/physiology ; p38 Mitogen-Activated Protein Kinases/*metabolism

This study was designed to examine how such factors as hemodialysis parameters, body mass index, renin and aldosterone concentrations, sympathetic nervous activity, and parathyroid hormone concentrations are associated with the control of hypertension in hemodialysis patients. Hemodialysis patients (n=114) were grouped into four categories. Group 1 had normal BP without antihypertensive medication. Group 2 needed one antihypertensive drug, Group 3 needed combination of two or three categories of antihypertensive drugs without minoxidil. Group 4 needed more than three categories of antihypertensive drugs including minoxidil. Parathyroid hormone, beta2-microglobulin, renin and aldosterone, epinephrine, norepinephrine, and hemodialysis parameters were measured. The fractional clearance of urea as Kt/V urea was significantly lower in Group 3 and Group 4 than in Group 2 (p<0.01). Concentrations of parathyroid hormone were significantly higher in Group 4 than the other groups (p<0.01). Pre-hemodialysis norepinephrine concentrations were significantly higher in Group 4 than the other groups (p<0.05). Traditional factors associated with hypertension did not seem to be relevant to the degree of hypertension in hemodialysis patients in the present study. In conclusion, poor Kt/V urea, elevated parathyroid hormone concentrations, and elevated concentrations of plasma norepinephrine seemed to be the factors that might be associated with control of hypertension in hemodialysis patients.
Adult ; Aged ; Aldosterone/*blood ; Analysis of Variance ; Antihypertensive Agents/therapeutic use ; Blood Pressure/drug effects/*physiology ; Epinephrine/blood ; Female ; Humans ; Hypertension/blood/drug therapy/physiopathology ; Kidney Failure, Chronic/blood/physiopathology/therapy ; Male ; Middle Aged ; Norepinephrine/blood ; Parathyroid Hormone/*blood ; *Renal Dialysis ; Renin/*blood ; Sympathetic Nervous System/*physiology ; Urea/metabolism

OBJECTIVETo compare the mRNA expression of renin-angiotensin-aldosterone system in human subcutaneous and visceral adipose tissues.

METHODSTotal RNA was extracted from 12 human subcutaneous adipose tissues, 12 perirenal adipose tissue and 9 periadrenal adipose tissues. The expressions of angiotensinogen ( AGT) , renin, angiotensin converting enzyme ( ACE) , angiotensin converting enzyme 2 (ACE2), angiotensin I1 receptor type 1 (AT1), angiotensin II receptor type 2 (AT2 ), CYP11 B2, and their internal reference glyceraldehyde phosphate (GAPDH) were studied by reverse transcription-polymerase chain reaction. The ratios of each target genes were used to evaluate the expression levels of AGT, renin, ACE, ACE2, AT1, AT2, and CYP11B2 in different adipose tissues.

RESULTSThe mRNA expressions of AGT, ACE, ACE2, AT1, and AT2 were detected in human subcutaneous, perirenal, and periadrenal adipose tissues. However, CYPI B2 mRNA expression was not found in these three adipose tissues. The mRNA expressions of renin was only detected in perirenal and periadrenal adipose tissues, which was significantly higher in perirenal adipose tissues than in periadrenal adipose tissues ( P < 0. 05 ). The mRNA expressions of ACE and ACE2 in perirenal adipose tissues were significantly higher than that in subcutaneous adipose tissues ( P < 0. 05). The mRNA expressions of ACE were significantly higher than that of ACE2 in subcutaneous, perirenal, and periadrenal adipose tissues (P <0. 05). The mRNA expressions of AT1 were significantly lower than that of AT2 in periadrenal adipose tissues (P < 0. 05).

CONCLUSIONLocal renin-angiotensin system exists in the adipose tissues; however, aldosterone is not synthesized in the adipose tissues.

Adipose Tissue ; metabolism ; Adult ; Aged ; Aldosterone ; physiology ; Angiotensinogen ; biosynthesis ; Cytochrome P-450 CYP11B2 ; biosynthesis ; Female ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; biosynthesis ; RNA, Messenger ; biosynthesis ; Receptor, Angiotensin, Type 1 ; biosynthesis ; Receptor, Angiotensin, Type 2 ; biosynthesis ; Renin ; biosynthesis ; Renin-Angiotensin System ; physiology ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the effect of astragaloside IV (As IV) on the activation of rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy.

METHODLeft ventricle hypertrophy was induced by abdominal aorta banding between bilateral renal aortas for 12 weeks. Rats were given astragaloside IV 1.0 mg x kg(-1) and 3.3 mg x kg(-1) for 12 weeks, respectively. After treatment, the left ventricular mass index (LVMI)was calculated by morphometry methods. Plasma and cardiac tissue angiotensin II, and plasma aldosterone were measured by ELISA method. Gene expressions of ACE, AT1 and AT2 in cardiac tissue were detected by real time PCR. Protein expressions of AT1 and AT2 in cardiac tissue were detected by Western blot.

RESULTCompared with model rats, LVMI was decreased by astragaloside IV treatment. Biochemical results indicated that the contents of angiotensin II in plasma and cardiac tissue as well as aldosterone in plasma were all increased in abdominal aorta banding rats comparing with sham-operated rats, then, decreased by astragaloside IV treatment. Gene expressions of cardiac ACE was downregulated by astragaloside IV, however, gene and protein expressions of cardiac AT2 were upregulated by astragaloside IV. Both elevated gene and protein expressions of AT1 were not attenuated by astragaloside IV.

CONCLUSIONExcessive activated rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy is inhibited by astragaloside IV treatment.

Aldosterone ; blood ; Angiotensin II ; blood ; metabolism ; Animals ; Blood Pressure ; physiology ; Cardiomegaly ; drug therapy ; Enzyme-Linked Immunosorbent Assay ; Hypertrophy, Left Ventricular ; drug therapy ; metabolism ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; genetics ; Receptor, Angiotensin, Type 2 ; genetics ; Renin-Angiotensin System ; drug effects ; Saponins ; therapeutic use ; Triterpenes ; therapeutic use