TY - JOUR
T1 - Cyclosporine nephrotoxicity in spontaneously hypertensive rats
AU - Stanley Nahman, N.
AU - Cosio, F. G.
AU - Mahan, J. D.
AU - Henry, M. L.
AU - Ferguson, R. M.
PY - 1988/4
Y1 - 1988/4
N2 - In the present study, we investigated the combined, nephrotoxic effects of cyclosporine (CsA) and hyperten-sion in young, spontaneously hypertensive rats (SHR). After 4 weeks of CsA therapy, SHR, compared with oil- treated SHR, showed an acceleration in the development of hypertension, mild renal insufficiency, and the accu-mulation of periodic-acid—Schiff—positive (PAS [+]) material in periglomerular arterioles. By electron microscopy, PAS(+) material was composed of intracy- toplasmic inclusion bodies consistent with the accumu-lation of renin granules. This finding was demonstrated in SHR after 4 weeks of CsA therapy but not after 8 weeks of therapy. By contrast, CsA had no significant effect on blood pressure in Wistar-Kyoto rats, a normo- tensive control. To investigate the effect of unilateral nephrectomy (UNx) on the development of renal histopathologic changes in this model, SHR were subjected to uninephrectomy and CsA or oil therapy. UNx accelerated the development of hypertension in all SHR groups. SHR subjected to UNx demonstrated no renal histopathologic changes after CsA or oil treatment. In conclusion, CsA accelerates the development of hypertension in SHR, and this effect is probably renin-me- diated. The combination of UNx and CsA therapy in the SHR does not result in significant renal histologic damage.
AB - In the present study, we investigated the combined, nephrotoxic effects of cyclosporine (CsA) and hyperten-sion in young, spontaneously hypertensive rats (SHR). After 4 weeks of CsA therapy, SHR, compared with oil- treated SHR, showed an acceleration in the development of hypertension, mild renal insufficiency, and the accu-mulation of periodic-acid—Schiff—positive (PAS [+]) material in periglomerular arterioles. By electron microscopy, PAS(+) material was composed of intracy- toplasmic inclusion bodies consistent with the accumu-lation of renin granules. This finding was demonstrated in SHR after 4 weeks of CsA therapy but not after 8 weeks of therapy. By contrast, CsA had no significant effect on blood pressure in Wistar-Kyoto rats, a normo- tensive control. To investigate the effect of unilateral nephrectomy (UNx) on the development of renal histopathologic changes in this model, SHR were subjected to uninephrectomy and CsA or oil therapy. UNx accelerated the development of hypertension in all SHR groups. SHR subjected to UNx demonstrated no renal histopathologic changes after CsA or oil treatment. In conclusion, CsA accelerates the development of hypertension in SHR, and this effect is probably renin-me- diated. The combination of UNx and CsA therapy in the SHR does not result in significant renal histologic damage.
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U2 - 10.1097/00007890-198804000-00020
DO - 10.1097/00007890-198804000-00020
M3 - Article
C2 - 3358277
AN - SCOPUS:0023944977
SN - 0041-1337
VL - 45
SP - 768
EP - 772
JO - Transplantation
JF - Transplantation
IS - 4
ER -