Glucocorticoids Suppress Growth in Neonatal Cardiomyocytes Co-Expressing AT2 and AT1 Angiotensin Receptors

Abstract

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 (AT₂) receptor co-expression with angiotensin II type 1 (AT₁) receptor is of specific importance in this modulatory function. Methods: In this study, we used AT₁ and AT₂ receptor-expressing adenoviruses (Ad-AT₁ and Ad-AT₂) 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 µmol/l) to neonatal cardiomyocytes infected with Ad-AT₁ alone, a significant growth response was measured (133.2 ± 4.8%). Expression of Ad-AT₂ alone induced a ∼20% increase in total cellular protein content, which was unaffected by addition of AngII. Neither corticosterone (1 µmol/l) nor dexamethasone (1 µmol/l) had any significant effect on the AT₁- or AT₂-mediated growth responses. In contrast, the growth response to AngII was augmented following co-expression of AT₂ and AT₁ receptors (149.2 ± 4.2%), which was reduced by ∼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 AT₂and AT₁ receptor subtypes are co-expressed.