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

Journal Article (Journal Article)

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 beta-adrenergic receptor density, suggesting that crosstalk between IGF-1 and beta-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.

Full Text

Duke Authors

Cited Authors

  • Lembo, G; Rockman, HA; Hunter, JJ; Steinmetz, H; Koch, WJ; Ma, L; Prinz, MP; Ross, J; Chien, KR; Powell-Braxton, L

Published Date

  • December 1, 1996

Published In

Volume / Issue

  • 98 / 11

Start / End Page

  • 2648 - 2655

PubMed ID

  • 8958230

Pubmed Central ID

  • PMC507725

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI119086


  • eng

Conference Location

  • United States