Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene.
Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin activity. We tested the hypothesis that these rats exhibit an increase in vascular angiotensin formation caused by the presence of the transgene. We measured the release of angiotensins I and II from isolated perfused hindquarters by high-performance liquid chromatography and radioimmunoassay. Female rats heterozygous for the transgene had significantly elevated mean arterial pressure compared with control rats (189.3 +/- 9.5 versus 110.0 +/- 5.4 mm Hg, p less than 0.05). Plasma angiotensin II was significantly decreased in transgenic rats. Transgenic rat hindquarters released more angiotensin I (121 +/- 37 versus 39 +/- 12 fmol/30 min, n = 7 each) and more angiotensin II (210 +/- 21 versus 62 +/- 12 fmol/30 min, p less than 0.05, n = 7 each) than control rat hindquarters. Captopril increased angiotensin I release and decreased angiotensin II values in both transgenic and control rat hindquarters. Bilateral nephrectomy 24 hours before hindquarter perfusion greatly reduced angiotensin release from control rat hindquarters but not from transgenic rat hind limbs. We also tested for the presence of Ren-2 messenger RNA in mesenteric and aortic tissue by RNase protection assay and Northern blot analysis. We found that Ren-2 messenger RNA was present in mesenteric and aortic tissue of transgenic but not of control rats. We conclude that the Ren-2 transgene is expressed in vascular tissue of transgenic rats and may be responsible for substantial increases in vascular angiotensin formation.
Hilgers
K F
KF
Department of Medicine-Nephrology, University of Erlangen-Nürnberg, FRG.
Peters
J
J
Veelken
R
R
Sommer
M
M
Rupprecht
G
G
Ganten
D
D
Luft
F C
FC
Mann
J F
JF
D000804:Angiotensin II / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000378:metabolism*; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D051379:Mice / Q000235:genetics*; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009392:Nephrectomy; D010477:Perfusion; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000235:genetics*
D012333:RNA, Messenger; D000804:Angiotensin II; D012083:Renin