Hemodynamics in Transgenic Mice With Overexpression of Atrial Natriuretic Factor

The circulatory effects associated with lifelong plasma atrial natriuretic factor (ANF) elevation were examined by generating transgenic mice, which constitutively express a fusion gene consisting of the transthyretin promoter and the ANF structural gene. These mice have chronically elevated ANF lev...

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Bibliographic Details
Published in:Circulation research 1994-04, Vol.74 (4), p.747-751
Main Authors: Barbee, R Wayne, Perry, Bret D, Re, Richard N, Murgo, Joseph P, Field, Loren J
Format: Article
Language:English
Subjects:
Animals
Atrial Natriuretic Factor - biosynthesis
Atrial Natriuretic Factor - genetics
Biological and medical sciences
Biotechnology
Fundamental and applied biological sciences. Psychology
Genetic engineering
Genetic technics
Hemodynamics
Male
Methods. Procedures. Technologies
Mice
Mice, Inbred C3H
Mice, Transgenic
Transgenic animals
Transgenic animals and transgenic plants
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Summary:The circulatory effects associated with lifelong plasma atrial natriuretic factor (ANF) elevation were examined by generating transgenic mice, which constitutively express a fusion gene consisting of the transthyretin promoter and the ANF structural gene. These mice have chronically elevated ANF levels as compared with their nontransgenic siblings. Transgenic animals exhibited immunoreactive ANF levels that were nearly fivefold higher than those measured in nontransgenic littermates. Systemic and regional hemodynamics and blood volumes were explored by using modifications of the reference microsphere and dilution techniques. Mean arterial pressure was reduced by 24 mm Hg, associated with a 27% reduction in total heart weight. This chronic reduction in blood pressure was due to a 21% reduction in total peripheral resistance, whereas cardiac output, stroke volume, and heart rate were not significantly altered, despite a 15% elevation in plasma volume. Transgenic mice displayed reductions of 35%, 33%, 32%, and 19% in muscle, skin, brain, and renal vascular resistance, respectively, whereas coronary and splanchnic resistances were not significantly altered. The findings complement earlier data from chronically infused normotensive mammals and suggest that these mice are an excellent model for investigating the effects of lifelong ANF elevation.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.74.4.747