TY - JOUR
T1 - Effect of Sulindac on Prostaglandin Synthesis in Human and in Cultured Rat Renal and Vascular Smooth Muscle Cells
AU - Sato, Makito
AU - Abe, Keishi
AU - Takeuchi, Kazuhisa
AU - Yasujima, Minoru
AU - Akiu, Naoki
AU - Saito, Takao
AU - Yoshinaga, Kaoru
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - To examine the hypothesis that Sulindac does not inhibit renal prostaglandin (PG) synthesis, we investigated the effects of Sulindac and other nonsteroidal anti-inflammatory drugs on PG synthesis in human and in cultured rat renal and vascular smooth muscle (VSM) cells. In 7 patients with chronic glomerular disease, creatinine clearance and proteinuria were not changed by Sulindac but were significantly reduced by diclofenac sodium. However, urinary excretion of PGE2 was decreased by both drugs. In cultured glomerular mesangial (GM), renal papillary collecting tubule (RPCT) and VSM cells from mesenteric artery, indomethacin, tiaprofenic acid, aspirin and ibuprofen inhibited both basal and arachidonic acid (AA)-stimulated PG synthesis dose-dependently. Although sulindac sulfoxide, at the same concentrations, inhibited both basal and AA-stimulated PGE2 synthesis in RPCT cells, it was less potent to inhibit PGI2 synthesis in VSM cells or PGE2 synthesis in GM cells. Active form sulindac sulfide inhibited PG synthesis in all types of cells but its inactive form sulfone did not. We conclude that sulindac inhibits renal PG synthesis but has little effect on renal function. This may be explained by its relatively weak potency on glomerular or vascular PG synthesis inhibition possibly due to the different biotransformation of the sulfoxide to the active sulfide in these cells.
AB - To examine the hypothesis that Sulindac does not inhibit renal prostaglandin (PG) synthesis, we investigated the effects of Sulindac and other nonsteroidal anti-inflammatory drugs on PG synthesis in human and in cultured rat renal and vascular smooth muscle (VSM) cells. In 7 patients with chronic glomerular disease, creatinine clearance and proteinuria were not changed by Sulindac but were significantly reduced by diclofenac sodium. However, urinary excretion of PGE2 was decreased by both drugs. In cultured glomerular mesangial (GM), renal papillary collecting tubule (RPCT) and VSM cells from mesenteric artery, indomethacin, tiaprofenic acid, aspirin and ibuprofen inhibited both basal and arachidonic acid (AA)-stimulated PG synthesis dose-dependently. Although sulindac sulfoxide, at the same concentrations, inhibited both basal and AA-stimulated PGE2 synthesis in RPCT cells, it was less potent to inhibit PGI2 synthesis in VSM cells or PGE2 synthesis in GM cells. Active form sulindac sulfide inhibited PG synthesis in all types of cells but its inactive form sulfone did not. We conclude that sulindac inhibits renal PG synthesis but has little effect on renal function. This may be explained by its relatively weak potency on glomerular or vascular PG synthesis inhibition possibly due to the different biotransformation of the sulfoxide to the active sulfide in these cells.
KW - nonsteroidal anti-inflammatory drug
KW - prostaglandin synthesis
KW - renal cells
KW - renal-sparing effect
KW - sulindac
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U2 - 10.1620/tjem.166.185
DO - 10.1620/tjem.166.185
M3 - Article
C2 - 1412444
AN - SCOPUS:0026769051
VL - 166
SP - 185
EP - 200
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
SN - 0040-8727
IS - 1
ER -