Aldosterone modulates cell proliferation and apoptosis in the neonatal rat heart.
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.
Sohn
Hyung Joo
HJ
Department of Pediatrics, Korea University College of Medicine, Korea University Hospital, Seoul, Korea.
Yoo
Kee Hwan
KH
Jang
Gi Young
GY
Lee
Jang Hoon
JH
Choi
Byung Min
BM
Lee
Jung Hwa
JH
Bae
In Sun
IS
Yim
Hyung Eun
HE
Son
Chang Sung
CS
Lee
Joo Won
JW
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
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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