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
Language
- eng
Conference Location
- United States