title: Aldosterone induces inflammatory cytokines in penile corpus cavernosum by activating the NF-κB pathway.
abstract: 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.
authors.affiliation: Department of Urology, Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Urology, Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Zu-Quan
authors.initials: ZQ
authors.lastname: Xiong
authors.affiliation: Department of Urology, Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Shan-Hua
authors.initials: SH
authors.lastname: Mao
authors.affiliation: Department of Urology, Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Ji-Meng
authors.initials: JM
authors.lastname: Hu
authors.affiliation: Department of Urology, Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: Department of Urology, Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Hao-Wen
authors.initials: HW
authors.lastname: Jiang
authors.affiliation: Department of Urology, Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D055785:Gene Knockdown Techniques; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D016328:NF-kappa B / Q000819:agonists* / Q000235:genetics; D010413:Penis / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D013148:Spironolactone / Q000494:pharmacology; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000450:Aldosterone; D016207:Cytokines; D051550:I-kappa B Kinase; D015850:Interleukin-6; D000451:Mineralocorticoid Receptor Antagonists; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C000628245:Il6 protein, rat