Cyclosporine nephrotoxicity in spontaneously hypertensive rats.
In the present study, we investigated the combined, nephrotoxic effects of cyclosporine (CsA) and hypertension 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 accumulation of periodic-acid-Schiff-positive (PAS [+]) material in periglomerular arterioles. By electron microscopy, PAS(+) material was composed of intracytoplasmic inclusion bodies consistent with the accumulation 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-mediated. The combination of UNx and CsA therapy in the SHR does not result in significant renal histologic damage.
Nahman
N S
NS
Department of Internal Medicine, Ohio State University, Columbus 43210.
Cosio
F G
FG
Mahan
J D
JD
Henry
M L
ML
Ferguson
R M
RM
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000633:toxicity*; D005260:Female; D006973:Hypertension / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D009392:Nephrectomy; D000069463:Olive Oil; D010938:Plant Oils / Q000008:administration & dosage; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects
D003524:Cyclosporins; D000069463:Olive Oil; D010938:Plant Oils; D003404:Creatinine