Decreased blood pressure response in mice deficient of the α(1b)- adrenergic receptor

A. Cavalli, A. L. Lattion, E. Hummler, M. Nenniger, T. Pedrazzini, F. Aubert J.-, M. C. Michel, M. Yang, G. Lembo, C. Vecchione, M. Mostardini, A. Schmidt, F. Beermann, S. Cotecchia

Research output: Contribution to journalArticlepeer-review

Abstract

To investigate the functional role of different α1-adrenergic receptor (α1-AR) subtypes in vivo, we have applied a gene targeting approach to create a mouse model lacking the α(1b)-AR (α(1b) -/-). Reverse transcription-PCR and ligand binding studies were combined to elucidate the expression of the α1-AR subtypes in various tissues of α(1b) +/+ and -/- mice. Total α1-AR sites were decreased by 98% in liver, 74% in heart, and 42% in cerebral cortex of the α(1b) -/- as compared with +/+ mice. Because of the large decrease of α1-AR in the heart and the loss of the α(1b)-AR mRNA in the aorta of the α(1b) -/- mice, the in vivo blood pressure and in vitro aorta contractile responses to α1-agonists were investigated in α(1b) +/+ and -/- mice. Our findings provide strong evidence that the α(1b)-AR is a mediator of the blood pressure and the aorta contractile responses induced by α1 agonists. This was demonstrated by the finding that the mean arterial blood pressure response to phenylephrine was decreased by 45% in α(1b) -/- as compared with +/+ mice. In addition, phenylephrine- induced contractions of aortic rings also were decreased by 25% in α(1b) - /- mice. The α(1b)-AR knockout mouse model provides a potentially useful tool to elucidate the functional specificity of different α1-AR subtypes, to better understand the effects of adrenergic drugs, and to investigate the multiple mechanisms involved in the control of blood pressure.

Original languageEnglish
Pages (from-to)11589-11594
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number21
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Genetics
  • General

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