title: Aldosterone modulates cell proliferation and apoptosis in the neonatal rat heart.
abstract: In the present study, we investigated whether and how the mineralocorticoid receptor antagonist spironolactone affects cardiac growth and development through apoptosis and cell proliferation in the neonatal rat heart. Newborn rat pups were treated with spironolactone (200 mg/kg/d) for 7 days. The cell proliferation was studied by PCNA immunostaining. The treatment with spironolactone decreased proliferating myocytes by 32% (P<0.05), and reduced myocytes apoptosis by 29% (P<0.05). Immunoblot and immunohistochemistry for the expression of p38, p53, clusterin, TGF-beta2, and extracellular signal-regulated kinase were performed. In the spironolactone group, p38, p53, clusterin, and TGF-beta2 protein expression was significantly decreased (P<0.05). These results indicate that aldosterone inhibition in the developing rat heart induces cardiac growth impairment by decreasing proliferation and apoptosis of myocytes.
authors.affiliation: Department of Pediatrics, Korea University College of Medicine, Korea University Hospital, Seoul, Korea.
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Sohn
authors.forename: Kee Hwan
authors.initials: KH
authors.lastname: Yoo
authors.forename: Gi Young
authors.initials: GY
authors.lastname: Jang
authors.forename: Jang Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Byung Min
authors.initials: BM
authors.lastname: Choi
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: In Sun
authors.initials: IS
authors.lastname: Bae
authors.forename: Hyung Eun
authors.initials: HE
authors.lastname: Yim
authors.forename: Chang Sung
authors.initials: CS
authors.lastname: Son
authors.forename: Joo Won
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D049109:Cell Proliferation; D051152:Clusterin / Q000235:genetics / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D051152:Clusterin; D000451:Mineralocorticoid Receptor Antagonists; D018809:Proliferating Cell Nuclear Antigen; D053781:Transforming Growth Factor beta2; D016159:Tumor Suppressor Protein p53; D013148:Spironolactone; D048051:p38 Mitogen-Activated Protein Kinases
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