Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency

Giuseppe Lembo, Howard A. Rockman, John J. Hunter, Hope Steinmetz, Walter J. Koch, Lan Ma, Morton P. Prinz, John Ross, Kenneth R. Chien, Lyn Powell-Braxton

Research output: Contribution to journalArticle

Abstract

To circumvent the embryonic lethality of a complete deficiency in insulin-like growth factor 1 (IGF-1), we generated mice homozygous for a site-specific insertional event that created a mutant IGF-1 allele (igf1m). These mice have IGF-1 levels 30% of wild type yet survive to adulthood, thereby allowing physiological analysis of the phenotype. Miniaturized catheterization technology revealed elevated conscious blood pressure in IGF- 1(m/m) mice, and measurements of left ventricular contractility were increased. Adenylyl cyclase activity was enhanced in IGF-1(m/m) hearts, without an increase in β-adrenergic receptor density, suggesting that crosstalk between IGF-1 and β-adrenergic signaling pathways may mediate the increased contractility. The hypertrophic response of the left ventricular myocardium in response to aortic constriction, however, was preserved in IGF- 1(m/m) mice. We conclude that chronic alterations in IGF-1 levels can selectively modulate blood pressure and left ventricular function, while not affecting adaptive myocardial hypertrophy in vivo.

Original languageEnglish
Pages (from-to)2648-2655
Number of pages8
JournalJournal of Clinical Investigation
Volume98
Issue number11
Publication statusPublished - Dec 1 1996

Keywords

  • β receptors
  • adrenergic receptors
  • hypertension
  • insulin-like growth factor I
  • mutagenesis, site-directed
  • myocardial contraction

ASJC Scopus subject areas

  • Medicine(all)

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    Lembo, G., Rockman, H. A., Hunter, J. J., Steinmetz, H., Koch, W. J., Ma, L., Prinz, M. P., Ross, J., Chien, K. R., & Powell-Braxton, L. (1996). Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency. Journal of Clinical Investigation, 98(11), 2648-2655.