Hypertension, Vol 16, 301-307, Copyright © 1990 by American Heart Association
ME Steinhelper, KL Cochrane and LJ Field
Chronic regulation of the cardiovascular system by atrial natriuretic
factor was investigated by generating transgenic mice with elevated hormone
levels in the systemic circulation. A fusion gene comprising the mouse
transthyretin promoter and mouse atrial natriuretic factor structural
sequences was designed so as to target hormone expression to the liver.
Hepatic expression of atrial natriuretic factor was detectable as early as
embryonic day 15 in transgenic animals. In adult transgenic mice, plasma
immunoreactive atrial natriuretic factor concentration was elevated at
least eightfold as compared with nontransgenic littermates. The mean
arterial pressure of conscious transgenic mice was 75.5 +/- 0.9 mm Hg,
significantly less than that of nontransgenic siblings (103.9 +/- 2.0 mm
Hg). This difference in mean arterial pressure was not accompanied by
significant changes in several other physiological parameters, including
heart rate, plasma and urinary electrolytes, water intake, and urine
volume. This study demonstrates that a chronic elevation of plasma atrial
natriuretic factor decreases arterial blood pressure without inducing
diuresis and natriuresis in transgenic mice and also illustrates the value
of the transgenic approach for the study of the cardiovascular system.
ARTICLES
Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes
Cold Spring Harbor Laboratory, NY 11724.
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