Cyclosporine nephrotoxicity in spontaneously hypertensive rats

Norris Stanley Nahman, F. G. Cosio, J. D. Mahan, M. L. Henry, R. M. Ferguson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)768-772
Number of pages5
JournalTransplantation
Volume45
Issue number4
StatePublished - Jan 1 1988
Externally publishedYes

Fingerprint

Inbred SHR Rats
Cyclosporine
Oils
Hypertension
Kidney
Renin
Therapeutics
Inbred WKY Rats
Inclusion Bodies
Arterioles
Nephrectomy
Renal Insufficiency
Electron Microscopy
Blood Pressure

ASJC Scopus subject areas

  • Transplantation

Cite this

Nahman, N. S., Cosio, F. G., Mahan, J. D., Henry, M. L., & Ferguson, R. M. (1988). Cyclosporine nephrotoxicity in spontaneously hypertensive rats. Transplantation, 45(4), 768-772.

Cyclosporine nephrotoxicity in spontaneously hypertensive rats. / Nahman, Norris Stanley; Cosio, F. G.; Mahan, J. D.; Henry, M. L.; Ferguson, R. M.

In: Transplantation, Vol. 45, No. 4, 01.01.1988, p. 768-772.

Research output: Contribution to journalArticle

Nahman, NS, Cosio, FG, Mahan, JD, Henry, ML & Ferguson, RM 1988, 'Cyclosporine nephrotoxicity in spontaneously hypertensive rats', Transplantation, vol. 45, no. 4, pp. 768-772.
Nahman NS, Cosio FG, Mahan JD, Henry ML, Ferguson RM. Cyclosporine nephrotoxicity in spontaneously hypertensive rats. Transplantation. 1988 Jan 1;45(4):768-772.
Nahman, Norris Stanley ; Cosio, F. G. ; Mahan, J. D. ; Henry, M. L. ; Ferguson, R. M. / Cyclosporine nephrotoxicity in spontaneously hypertensive rats. In: Transplantation. 1988 ; Vol. 45, No. 4. pp. 768-772.
@article{35311d4a537e4690865c3cfe3b766ac6,
title = "Cyclosporine nephrotoxicity in spontaneously hypertensive rats",
abstract = "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.",
author = "Nahman, {Norris Stanley} and Cosio, {F. G.} and Mahan, {J. D.} and Henry, {M. L.} and Ferguson, {R. M.}",
year = "1988",
month = "1",
day = "1",
language = "English (US)",
volume = "45",
pages = "768--772",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Cyclosporine nephrotoxicity in spontaneously hypertensive rats

AU - Nahman, Norris Stanley

AU - Cosio, F. G.

AU - Mahan, J. D.

AU - Henry, M. L.

AU - Ferguson, R. M.

PY - 1988/1/1

Y1 - 1988/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=0023944977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023944977&partnerID=8YFLogxK

M3 - Article

C2 - 3358277

AN - SCOPUS:0023944977

VL - 45

SP - 768

EP - 772

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 4

ER -