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Inhibition of medullary prostaglandin E2 (PGE2) by non‐steroidal anti‐inflammatory drugs (NSAIDs) adversely affects medullary blood flow
Author(s) -
Kennedy-Lydon Teresa M,
Crawford Carol,
Sawbridge Liam,
Unwin Robert J,
Wildman Scott SP,
Peppiatt-Wildman Claire M
Publication year - 2012
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.26.1_supplement.690.9
Subject(s) - vasa recta , pericyte , bradykinin , vasodilation , kidney , nephrotoxicity , vasa vasorum , prostaglandin e2 , chemistry , endocrinology , prostaglandin , microcirculation , medicine , receptor , endothelial stem cell , biochemistry , in vitro
NSAIDs are known to be nephrotoxic and act to inhibit cyclooxygenases (COX) and thus production of PGE 2 . Here we use the kidney slice model to investigate (i) the effect of PGE 2 on in situ vasa recta pericytes (ii) the ability of PGE 2 to attenuate ET‐1 and Ang‐II‐evoked vasoconstriction of vasa recta, (iii) the effect of NSAIDs on in situ vasa recta pericytes, and (iv) whether NSAIDs attenuate PGE 2 and bradykinin‐mediated vasa recta dilation. Kidney slices were collected as previously described 1 . Real‐time images of in situ vasa recta were recorded and vasa recta diameter at pericyte and non‐pericyte sites measured off‐line. PGE 2 evoked dilation of vasa recta specifically at pericyte sites and significantly attenuated pericyte‐mediated constriction of vasa recta evoked by both ET‐1 and Ang‐II. NSAIDs, indomethacin>SC560> celecoxib>meloxicam, evoked significantly greater constriction of vasa recta capillaries at pericyte sites than at non‐pericyte sites and indomethacin significantly attenuated the pericyte‐mediated vasodilation of vasa recta evoked by both PGE 2 and bradykinin. These data indicate PGE 2 is key in attenuating vasa recta diameter and thus medullary blood flow (MBF). Inhibition of PGE 2 that occurs during chronic NSAID treatment causes constriction of vasa recta by pericytes. Thus pericytes may be key in NSAID‐evoked reduction in MBF and any ensuing nephrotoxicity.