Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency.
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.
Lembo
G
G
Department of Medicine, University of California, San Diego, La Jolla 92093, USA.
Rockman
H A
HA
Hunter
J J
JJ
Steinmetz
H
H
Koch
W J
WJ
Ma
L
L
Prinz
M P
MP
Ross
J
J
Chien
K R
KR
Powell-Braxton
L
L
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
D001786:Blood Glucose; D017931:DNA Primers; D011943:Receptors, Adrenergic, beta; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D000262:Adenylyl Cyclases