Endothelin-1 and angiotensin II contribute to BNP but not c-fos gene expression response to elevated load in isolated mice hearts.
The early events in the cardiac hypertrophic process induced by hemodynamic load include activation of B-type natriuretic peptide (BNP) and c-fos gene expression. However, it is unknown whether stretch acts directly or through local paracrine factors to trigger changes in cardiac gene expression. Herein we studied the involvement of endothelin-1 (ET-1) and angiotensin II (Ang II) in load-induced activation of left ventricular BNP and c-fos gene expression using an in vitro stretch model in isolated perfused adult mice hearts. Two-hour stretch induced by increasing coronary flow rate from 2 to 5 ml/min increased the expression of BNP and c-fos genes by 1.9- and 1.5-fold, respectively (P<0.001 and P<0.05). A mixed ET(A/B) receptor antagonist bosentan attenuated the BNP gene expression response to load by 58% (P<0.005). A similar 53% inhibition was observed with the selective ET(A) receptor blocker BQ-123 (P<0.05). Type 1 Ang II receptor antagonist CV-11974 decreased the activation of BNP gene expression by 50% (P<0.05). In contrast, the activation of c-fos gene expression was not inhibited by antagonists of ET(A/B) and AT(1) receptors. Our results show that ET-1 and Ang II play a key role in the induction of BNP, but not c-fos gene expression in response to load in intact adult murine hearts.
Piuhola
Jarkko
J
Department of Pharmacology and Toxicology, Faculty of Medicine, Biocenter Oulu, University of Oulu PO Box 5000, FIN-90014 University of Oulu, Finland.
Szokodi
István
I
Ruskoaho
Heikki
H
D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D003326:Coronary Circulation; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D016762:Genes, fos; D006321:Heart / Q000502:physiology; D006352:Heart Ventricles / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D020097:Natriuretic Peptide, Brain / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; C081643:candesartan