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Nonsteroidal anti-inflammatory drugs alter vasa recta diameter via pericytes

Kennedy-Lydon, Teresa, Crawford, Carol, Wildman, Scott S.P., Peppiatt-Wildman, Claire M. (2015) Nonsteroidal anti-inflammatory drugs alter vasa recta diameter via pericytes. American Journal of Physiology - Renal Physiology, 309 (7). F648-F657. ISSN 1931-857X. E-ISSN 1522-1466. (doi:10.1152/ajprenal.00199.2015) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://doi.org/10.1152/ajprenal.00199.2015

Abstract

We have previously shown that vasa recta pericytes are known to dilate vasa recta capillaries in the presence of PGE2 and contract vasa recta capillaries when endogenous production of PGE2 is inhibited by the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin. In the present study, we used a live rat kidney slice model to build on these initial observations and provide novel data that demonstrate that nonselective, cyclooxygenase-1-selective, and cyclooxygenase -2-selective NSAIDs act via medullary pericytes to elicit a reduction of vasa recta diameter. Real-time images of in situ vasa recta were recorded, and vasa recta diameters at pericyte and nonpericyte sites were measured offline. PGE2 and epoprostenol (a prostacyclin analog) evoked dilation of vasa recta specifically at pericyte sites, and PGE2 significantly attenuated pericyte-mediated constriction of vasa recta evoked by both endothelin-1 and ANG II. NSAIDs (indomethacin > SC-560 > celecoxib > meloxicam) evoked significantly greater constriction of vasa recta capillaries at pericyte sites than at nonpericyte sites, and indomethacin significantly attenuated the pericyte-mediated vasodilation of vasa recta evoked by PGE2, epoprostenol, bradykinin, and S-nitroso-N-acetyl-l-penicillamine. Moreover, a reduction in PGE2 was measured using an enzyme immune assay after superfusion of kidney slices with indomethacin. In addition, immunohistochemical techiques were used to demonstrate the population of EP receptors in the medulla. Collectively, these data demonstrate that pericytes are sensitive to changes in PGE2 concentration and may serve as the primary mechanism underlying NSAID-associated renal injury and/or further compound-associated tubular damage.

Item Type: Article
DOI/Identification number: 10.1152/ajprenal.00199.2015
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 13 Dec 2015 15:26 UTC
Last Modified: 29 May 2019 16:42 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53101 (The current URI for this page, for reference purposes)
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