Engineering the cardiovascular system. Blood pressure regulation

Steinhelper, M. E., Cochrane, K. L., Field, L. J. (December 1991) Engineering the cardiovascular system. Blood pressure regulation. Ann N Y Acad Sci, 646. pp. 248-53. ISSN 0077-8923 (Print)0077-8923 (Linking)

DOI: 10.1111/j.1749-6632.1991.tb18587.x


We have generated several lineages of transgenic mice that exhibit chronic elevations in the steady-state concentration of atrial natriuretic factor (ANF) in the peripheral circulation. ANF, a peptide hormone synthesized primarily by atrial cardiomyocytes, is a potent natriuretic and diuretic. ANF also reduces blood pressure transiently when acutely administered. To address the potential role of ANF in chronic cardiovascular regulation, we generated transgenic mice that express the ANF gene in the liver. The fusion genes comprised either the mouse transthyretin (TTR) or rat phosphoenolpyruvate carboxykinase (PEPCK) promoters fused to the mouse ANF structural gene and were designed to target to the liver constitutive and inducible expression of pre-pro-ANF, respectively. Transgenic animals harboring the TTR-ANF fusion gene expressed chimeric ANF transcripts exclusively in the liver. In contrast, mice harboring the PEPCK-ANF fusion gene did not express detectable amounts of ANF mRNA in liver even after induction (24-hour fasting). In the TTR-ANF mice, hepatic and plasma immunoreactive ANF concentrations were proportional to the concentration of hepatic ANF transcripts. Moreover, mean arterial blood pressure recorded in conscious transgenic mice was inversely proportional to hepatic ANF expression. These transgenic models demonstrate that chronically elevated ANF concentration can induce sustained hypotension.

Item Type: Paper
Uncontrolled Keywords: Animals Atrial Natriuretic Factor/genetics/*physiology *Blood Pressure *Cardiovascular Physiological Phenomena Cloning, Molecular Female *Genetic Engineering Genetic Linkage Liver/metabolism Male Mice Mice, Transgenic Pedigree Phosphoenolpyruvate Carboxykinase (GTP)/genetics Prealbumin/genetics X Chromosome
Subjects: diseases & disorders > cardiovascular diseases
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
CSHL Authors:
Communities: CSHL labs
CSHL labs > Stillman lab
Depositing User: Matt Covey
Date: 27 December 1991
Date Deposited: 11 Jan 2016 15:46
Last Modified: 11 Jan 2016 15:46
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