doi: 10.1161/hy0202.103418
(Hypertension. 2002;39:629.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Lower Blood Pressure in Floxed Angiotensinogen Mice After Adenoviral Delivery of Cre-Recombinase
From the Departments of Internal Medicine and Physiology & Biophysics, The University of Iowa College of Medicine, Iowa City, Iowa.
Correspondence to Curt D. Sigmund, PhD, Chair, Molecular Biology Interdisciplinary Program, Director, Transgenic and Gene Targeting Facility, Department of Internal Medicine and Physiology & Biophysics, 2191 Medical Laboratory, The University of Iowa College of Medicine, Iowa City, IA 52242. E-mail curt-sigmund{at}uiowa.edu
Recent experimental evidence suggests a role for tissue renin-angiotensin systems in the development of hypertension. To test the importance of tissue renin-angiotensin systems in the development and maintenance of angiotensin II-dependent hypertension, we generated a transgenic model in which exon 2 of the human angiotensinogen gene is flanked by loxP sites (hAGTflox) so that this region of the gene can be deleted by the cre-recombinase. Double transgenic human renin and hAGTflox (R+/A+flox) mice of two independent lines exhibited elevated blood pressure. Acute administration of an adenovirus containing cre-recombinase (Adcre) lowered blood pressure by 30 mm Hg over a 4-day period as measured with fluid filled catheters. The chronic effect of Adcre administration on blood pressure was determined by radiotelemetry in a separate group of R+/A+flox mice. Blood pressure decreased by 25 mm Hg from baseline by day 8 post-Adcre, but increased on each day thereafter until it was 90% of baseline by day 21 post-Adcre. Expression analysis indicated the absence of detectable hAGT mRNA in the liver at day 5 post-Adcre, but reappeared at normal levels at days 14 to 21 post-Adcre. These studies suggest that Adcre is effective for acute, but not chronic, elimination of hepatic hAGT. Chronic elimination of hepatic hAGT will likely require the use of transgenic mice endogenously expressing cre-recombinase in the liver.
Key Words: gene expression • mice • renin-angiotensin system
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