Hypertension, Vol 19, 681-686, Copyright © 1992 by American Heart Association
M Bader, Y Zhao, M Sander, MA Lee, J Bachmann, M Bohm, B Djavidani, J Peters, JJ Mullins and D Ganten
A transgenic rat line, TGR(mREN2)27, was established by introducing the
murine Ren-2 gene into the genome of rats by microinjection techniques.
These rats exhibit severe hypertension, making them an interesting model in
which to study the role of renin in the pathophysiology of hypertension.
However, although the additional renin gene is the only genetic difference
compared with control rats, the exact mechanism of hypertension in
TGR(mREN2)27 rats is still unclear. It cannot be attributed to a
stimulation of the endocrine renin-angiotensin system or to an
overexpression of renin in the kidney, since plasma and kidney renin and
renin gene expression in the kidney are low in these animals. Here we
describe recent progress made toward elucidating mechanisms of hypertension
in TGR(mREN2)27 rats. 1) TGR(mREN2)27 rats were bred to homozygosity. The
development of high blood pressure in homozygous rats is accelerated
compared with that of heterozygous rats. This is paralleled by a higher
mortality rate in homozygous TGR(mREN2)27 rats. Blood pressure and
mortality rate of homozygous transgenic rats were effectively reduced by 10
mg captopril per kilogram body weight. 2) Treatment of 8-week-old
heterozygous TGR(mREN2)27 rats with 10 mg/kg body wt per day of the
angiotensin II receptor antagonist DuP 753 for 4.5 weeks normalized blood
pressure. After withdrawal of the drug, blood pressure increased rapidly,
reaching control levels after 3 weeks. In another group of TGR(mREN2)27
rats treated with 0.5 mg/kg per day, there was no change in blood pressure.
Plasma renin and plasma angiotensin II were significantly higher in the
high-dose group compared with the low-dose group.(ABSTRACT TRUNCATED AT 250
WORDS)
ARTICLES
Role of tissue renin in the pathophysiology of hypertension in TGR(mREN2)27 rats
German Institute for High Blood Pressure Research Heidelberg, FRG.
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