Role of tissue renin in the pathophysiology of hypertension in TGR(mREN2)27 rats.
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)
Bader
M
M
German Institute for High Blood Pressure Research Heidelberg, FRG.
Zhao
Y
Y
Sander
M
M
Lee
M A
MA
Bachmann
J
J
Böhm
M
M
Djavidani
B
B
Peters
J
J
Mullins
J J
JJ
Ganten
D
D
D000305:Adrenal Cortex Hormones / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D030801:Animals, Genetically Modified / Q000097:blood / Q000235:genetics / Q000502:physiology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015870:Gene Expression; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012083:Renin / Q000235:genetics / Q000502:physiology*; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D012083:Renin; D019808:Losartan