title: Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency.
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 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.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093, USA.
authors.forename: G
authors.initials: G
authors.lastname: Lembo
authors.forename: H A
authors.initials: HA
authors.lastname: Rockman
authors.forename: J J
authors.initials: JJ
authors.lastname: Hunter
authors.forename: H
authors.initials: H
authors.lastname: Steinmetz
authors.forename: W J
authors.initials: WJ
authors.lastname: Koch
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: M P
authors.initials: MP
authors.lastname: Prinz
authors.forename: J
authors.initials: J
authors.lastname: Ross
authors.forename: K R
authors.initials: KR
authors.lastname: Chien
authors.forename: L
authors.initials: L
authors.lastname: Powell-Braxton
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D017931:DNA Primers; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D009200:Myocardial Contraction; D010902:Pituitary Gland / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D001786:Blood Glucose; D017931:DNA Primers; D011943:Receptors, Adrenergic, beta; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D000262:Adenylyl Cyclases