Cardiomyocyte-Specific Endothelin A Receptor Knockout Mice Have Normal Cardiac Function and an Unaltered Hypertrophic Response to Angiotensin II and Isoproterenol

Rafal M. Kedzierski, Paul A. Grayburn, Yaz Y. Kisanuki, Clay S. Williams, Robert E Hammer, James A Richardson, Micheal D. Schneider, Masashi Yanagisawa

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Even though endothelin is recognized as an important vasoregulatory molecule, the roles of endothelin receptors in specific cell types are not yet fully understood. Mice with a null mutation in endothelin A receptor gene (ETA) or in the gene of its ligand (endothelin 1) die neonatally due to craniofacial and cardiac abnormalities. This early lethality has in the past hindered studies on the role of endothelin in cardiovascular physiology and pathophysiology. To overcome this obstacle, we utilized the cre/loxP technology to generate mice in which the ETA gene could be deleted specifically in cardiomyocytes. The cre recombinase transgene driven by the α-myosin heavy-chain promoter deleted the floxed ETA allele specifically in the hearts of these mice, resulting in a 78% reduction in cardiac ET A mRNA level compared to wild-type controls. Cardiomyocyte-specific ETA knockout animals are viable and exhibit normal growth, cardiac anatomy, and cardiac contractility, as assessed by echocardiography. In addition, these animals exhibit hypertrophic and contractile responses to 10-day infusion of angiotensin II or isoproterenol similar to those observed in control animals. These results indicate that in adult mice cardiac ET A receptors are not necessary for either baseline cardiac function or stress-induced response to angiotensin II or isoproterenol.

Original languageEnglish (US)
Pages (from-to)8226-8232
Number of pages7
JournalMolecular and cellular biology
Volume23
Issue number22
DOIs
StatePublished - Nov 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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