Glucocorticoids suppress growth in neonatal cardiomyocytes co-expressing AT(2) and AT(1) 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 (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 micromol/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 micromol/l) nor dexamethasone (1 micromol/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.

• Authors: Enzo R Porrello, William F Meeker, Walter G Thomas, Robert E Widdop, Lea M D Delbridge
• Journal: Neonatology (Neonatology) Vol. 97 Issue 3 Pg. 257-65 ( 2010) ISSN: 1661-7819 [Electronic] Switzerland
• PMID: 19887855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 S. Karger AG, Basel.

Chemical References

• Glucocorticoids
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Phenylephrine
• Dexamethasone
• Corticosterone

Topics

• Animals
• Animals, Newborn
• Cell Proliferation (drug effects)
• Cells, Cultured
• Corticosterone (administration & dosage, pharmacology)
• Dexamethasone (pharmacology)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Drug Antagonism
• Gene Expression (drug effects, physiology)
• Glucocorticoids (administration & dosage, pharmacology)
• Myocytes, Cardiac (drug effects, metabolism, physiology)
• Phenylephrine (administration & dosage, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Angiotensin, Type 1 (genetics, metabolism)
• Receptor, Angiotensin, Type 2 (genetics, metabolism)
• Transduction, Genetic