Pathophysiology of vascular smooth muscle in renin promoter-T-antigen transgenic mice.
The pathophysiological consequence of targeted production of SV-40 T-antigen to renin-expressing cells in the kidney of transgenic mice is reported. A histopathologic analysis of the kidney from adult transgenic mice (12-16 wk old) revealed the presence of severe vascular lesions manifested by marked atypical hyperplasia of vascular smooth muscle. The levels of plasma renin, kidney renin, and kidney renin mRNA were examined in 6- and 9-wk-old transgenic mice and were found to be significantly lower than their age-matched non-transgenic littermates and were nonresponsive to captopril treatment. However, there was no significant difference in conscious mean arterial pressure between transgenic and non-transgenic mice. The levels of renal renin mRNA in transgenics and nontransgenic littermates were compared throughout ontogeny and were found to be equal in newborns, elevated 3- to 5-fold in 1-wk-old transgenics, and yet decreased 10-fold by 6 wk of age in transgenic mice. Expression of the transgene in the kidney exhibited the proper developmental pattern and was properly restricted to juxtaglomerular cells in neonatal mice. Nevertheless, in adult mice, T-antigen-containing cells were found throughout the entire renal arterial tree. The observed ability of renal vascular cells to be recruited to express both renin and T-antigen suggests a mechanism that can explain the development of the renal pathology in these mice.
Duke Scholars
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tissue Distribution
- Renin
- RNA, Messenger
- Promoter Regions, Genetic
- Muscle, Smooth, Vascular
- Mice, Transgenic
- Mice
- Kidney
- Cardiovascular System & Hematology
- Captopril
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tissue Distribution
- Renin
- RNA, Messenger
- Promoter Regions, Genetic
- Muscle, Smooth, Vascular
- Mice, Transgenic
- Mice
- Kidney
- Cardiovascular System & Hematology
- Captopril