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A pivotal role for pericytes in non‐steroidal anti‐inflammatory drug‐induced toxicity
Author(s) -
PeppiattWildman Claire M,
KennedyLydon Teresa,
Crawford Carol,
Wildman Scott S P
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1110.17
Subject(s) - nephrotoxicity , vasodilation , vasa recta , pericyte , pharmacology , kidney , cyclooxygenase , inflammation , medicine , endogeny , chemistry , endocrinology , enzyme , endothelial stem cell , biochemistry , in vitro
Pericytes regulate vasa recta diameter in response to numerous endogenous vasoactive agents [1] and in so doing regulate medullary blood flow (MBF). Renal pericytes have also been implicated in numerous forms of kidney disease. Non‐steroidal anti‐inflammatory drugs (NSAIDs), routinely prescribed to alleviate pain and inflammation, have established nephrotoxic side effects, such as reduced MBF, that are often associated with chronic renal disease. NSAIDs inhibit cyclooxygenase (COX) enzymes and the production of endogenous vasodilatory prostanoids, which we have previously shown to exert their effects on vasa recta diameter via their action at pericytes. We propose renal pericytes are pivotal in NSAID‐mediated reduction in MBF and associated nephrotoxicity. We have utilized the live kidney slice model [1] to demonstrate NSAID‐mediated reduction in vasa recta diameter occurs specifically at pericytes and have identified NSAID‐mediated inhibition of vasodilatory PGE 2 and PGI 2 as critical in this process. We identify renal tubules as the source of vasodilatory prostanoids and suggest pericyte‐mediated tubulovascular cross‐talk mechanisms are vital for MBF regulation, and dysregulation of tubulovascular cross‐talk is central in NSAID‐associated nephrotoxicity.