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 (igf1(m)). 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.

Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency / Lembo, Giuseppe; H. A., Rockman; J. J., Hunter; H., Steinmetz; W. J., Koch; L., Ma; M. P., Prinz; J., Ross; K. R., Chien; L., Powell Braxton. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - STAMPA. - 98:11(1996), pp. 2648-2655. [10.1172/jci119086]

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

LEMBO, Giuseppe;
1996

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 (igf1(m)). 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.
1996
adrenergic receptors; beta receptors; cuore; hypertension; igf-1; insulin-like growth factor i; ipertensione; mutagenesis; site-directed; myocardial contraction; β receptors
01 Pubblicazione su rivista::01a Articolo in rivista
Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency / Lembo, Giuseppe; H. A., Rockman; J. J., Hunter; H., Steinmetz; W. J., Koch; L., Ma; M. P., Prinz; J., Ross; K. R., Chien; L., Powell Braxton. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - STAMPA. - 98:11(1996), pp. 2648-2655. [10.1172/jci119086]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/128292
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