OBJECTIVETo investigate the mRNA and protein expression of mineralocorticoid receptor (MR) in patients with atrial fibrillation.

METHODSTwenty-five patients with rheumatic heart valve disease, 12 in sinus rhythm and 13 in chronic atrial fibrillation (>or= 6 months), underwent transthoracic echocardiography and right and left atrial lateral wall tissue samples were obtained from these patients during mitral/aortic valve replacement operation. Realtime quantitative PCR and Western blot were used to determine the mRNA and protein expression of MR in atria specimens. The distribution of MR in human atria was analyzed by specific immunohistochemical staining.

RESULTSThe left atrial diameters increased markedly in atrial fibrillation group compared with that in sinus rhythm group (P<0.01). And the results showed that the level of mRNA and protein of MR were increased significantly in atrial fibrillation group compared with those in sinus rhythm group (P<0.01 or 0.05), whereas the expression of mRNA and protein of MR were found to be no difference between left atria and right atria both in fibrillation and sinus groups (all P>0.05). The special immunohistochemical staining demonstrated that MR was abundant in the human atrial myocardium and MRs were located mainly in the cytoplasm of atrial cells, which were more evident in atrial fibrillation group than those in sinus rhythm group.

CONCLUSIONThese findings suggested that MRs were upregulated in atrial fibrillation and aldosterone antagonists may be effective in treating atrial fibrillation.

Adult ; Atrial Fibrillation ; metabolism ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; RNA, Messenger ; genetics ; Receptors, Mineralocorticoid ; metabolism

Emerging evidence indicates that aldosterone and mineralocorticoid receptors (MRs) are associated with the pathogenesis of erectile dysfunction. However, the molecular mechanisms remain largely unknown. In this study, freshly isolated penile corpus cavernosum tissue from rats was treated with aldosterone, with or without MRs inhibitors. Nuclear factor (NF)-kappa B (NF-κB) activity was evaluated by real-time quantitative PCR, luciferase assay, and immunoblot. The results demonstrated that mRNA levels of the NF-κB target genes, including inhibitor of NF-κB alpha (IκB-α), NF-κB1, tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), were higher after aldosterone treatment. Accordingly, phosphorylation of p65/RelA, IκB-α, and inhibitor of NF-κB kinase-β was markedly increased by aldosterone. Furthermore, knockdown of MRs prevented activation of the NF-κB canonical pathway by aldosterone. Consistent with this finding, ectopic overexpression of MRs enhanced the transcriptional activation of NF-κB by aldosterone. More importantly, the MRs antagonist, spironolactone blocked aldosterone-mediated activation of the canonical NF-κB pathway. In conclusion, aldosterone has an inflammatory effect in the corpus cavernosum penis, inducing NF-κB activation via an MRs-dependent pathway, which may be prevented by selective MRs antagonists. These data reveal the possible role of aldosterone in erectile dysfunction as well as its potential as a novel pharmacologic target for treatment.
Aldosterone/pharmacology* ; Animals ; Cytokines/biosynthesis* ; Gene Knockdown Techniques ; I-kappa B Kinase/antagonists & inhibitors* ; Interleukin-6/genetics* ; Male ; Mineralocorticoid Receptor Antagonists/pharmacology* ; NF-kappa B/genetics* ; Penis/metabolism* ; Protein Serine-Threonine Kinases/antagonists & inhibitors* ; RNA, Messenger/biosynthesis* ; Rats ; Rats, Inbred WKY ; Receptors, Mineralocorticoid/genetics* ; Signal Transduction/drug effects* ; Spironolactone/pharmacology* ; Transcriptional Activation ; Tumor Necrosis Factor-alpha/biosynthesis* ; NF-kappaB-Inducing Kinase

BACKGROUNDA bioactive compound from Paecilomyces tenuipes (BCPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress (CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis.

METHODSThe antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21. Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone (CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test.

RESULTSChronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR.

CONCLUSIONSBCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.

Animals ; Antidepressive Agents ; pharmacology ; Chronic Disease ; Corticotropin-Releasing Hormone ; genetics ; Hydrocortisone ; blood ; Hypothalamo-Hypophyseal System ; drug effects ; physiology ; Male ; Monoamine Oxidase Inhibitors ; pharmacology ; Paecilomyces ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; genetics ; Receptors, Mineralocorticoid ; genetics ; Stress, Psychological ; physiopathology ; Sucrose ; administration & dosage

OBJECTIVETo investigate the effect of losartan on cardiac mineralocorticoid receptor (MR) mRNA in rats after acute myocardial infarction (AMI).

METHODAMI was induced in male SD rats by ligation of the left coronary artery. The survived rats were randomly divided into AMI group, losartan group, and sham-operated group. The cardiac functions of the rats were assessed by echocardiogram and hemodynamics, and the contents of angiotensin II (Ang II) and aldosterone (Ald) in the myocardial tissues were determined by radioimmunoassay. The collagen density in the myocardial tissues were calculated by Masson's trichrome staining and the expression of MR mRNA were determined by real-time quantitative fluorescent PCR.

RESULTSBoth the contents of AngII and Ald in the myocardial tissues increased significantly in AMI group compared with those in the sham-operated group (P<0.01). The expression of MR mRNA and collagen density in the myocardial tissues also increased significantly than that in sham-operated group (P<0.01). After four weeks of losartan treatment, the contents of AngII and Ald in the myocardial tissues decreased significantly (P<0.05) and the expression of MR mRNA was also considerably lowered (P<0.01) in comparison with those in the AMI group. Treatment with losartan also resulted in significant decrease of the collagen density in the myocardial tissues.

CONCLUSIONSLosartan may reduce reactive fibrosis not only by attenuating the Ald signaling pathway but also by decreasing the expression of MR.

Aldosterone ; metabolism ; Angiotensin II ; metabolism ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Fibrosis ; etiology ; prevention & control ; Losartan ; therapeutic use ; Male ; Myocardial Infarction ; drug therapy ; metabolism ; Myocardium ; pathology ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Mineralocorticoid ; genetics ; metabolism