Glucocorticoids suppress growth in neonatal cardiomyocytes co-expressing AT2 and AT1 angiotensin receptors

Enzo R Porrello, William F Meeker, Walter Glen Thomas, Robert Edward Widdop, Leanne MD Delbridge

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6 Citations (Scopus)


Background: Perinatal glucocorticoid treatment is associated with hypertrophic cardiomyopathy, but the cellular mechanism is controversial. An underlying interaction between glucocorticoids and the renin-angiotensin system may be important, but whether glucocorticoids modulate angiotensin II (AngII)-dependent cardiomyocyte growth responses in the neonate has not been investigated. Objectives: The major aim of this investigation was to determine whether glucocorticoids modulate the neonatal cardiomyocyte growth response to AngII. In particular we sought evidence to determine whether angiotensin II type 2 (AT(2)) receptor co-expression with angiotensin II type 1 (AT(1)) receptor is of specific importance in this modulatory function. Methods: In this study, we used AT(1) and AT(2) receptor-expressing adenoviruses (Ad-AT(1) and Ad-AT(2)) in a well-defined in vitro neonatal cardiomyocyte culture model to assess whether glucocorticoids affect cardiomyocyte growth responses (i.e. total protein content). Results: Following addition of AngII (0.1 mumol/l) to neonatal cardiomyocytes infected with Ad-AT(1) alone, a significant growth response was measured (133.2 +/- 4.8 ). Expression of Ad-AT(2) alone induced a approximately 20 increase in total cellular protein content, which was unaffected by addition of AngII. Neither corticosterone (1 mumol/l) nor dexamethasone (1 mumol/l) had any significant effect on the AT(1)- or AT(2)-mediated growth responses. In contrast, the growth response to AngII was augmented following co-expression of AT(2) and AT(1) receptors (149.2 +/- 4.2 ), which was reduced by approximately 20 in the presence of either corticosterone or dexamethasone (p <0.05). Conclusions: The present study provides novel evidence that glucocorticoids suppress neonatal cardiomyocyte growth responsiveness when AT(2 )and AT(1) receptor subtypes are co-expressed.
Original languageEnglish
Pages (from-to)257 - 265
Number of pages9
Issue number3
Publication statusPublished - 2010

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