Nonsteroidal anti-inflammatory drugs alter vasa recta diameter via pericytes
Autor: | Scott S.P. Wildman, Teresa M Kennedy-Lydon, Claire M. Peppiatt-Wildman, Carol Crawford |
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Rok vydání: | 2015 |
Předmět: |
Male
medicine.medical_specialty Physiology medicine.drug_class Vasodilator Agents Bradykinin Vasodilation In Vitro Techniques Biology Nitric Oxide Anti-inflammatory Renal Circulation Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals Drug Interactions Nonsteroidal urogenital system Anti-Inflammatory Agents Non-Steroidal Vasa recta Articles Capillaries Rats Cell biology Sprague dawley Kidney Tubules medicine.anatomical_structure Endocrinology chemistry Vasoconstriction Prostaglandins cardiovascular system Pericyte Pericytes Kidney tubules |
Zdroj: | American Journal of Physiology-Renal Physiology. 309:F648-F657 |
ISSN: | 1522-1466 1931-857X |
DOI: | 10.1152/ajprenal.00199.2015 |
Popis: | We have previously shown that vasa recta pericytes are known to dilate vasa recta capillaries in the presence of PGE2and contract vasa recta capillaries when endogenous production of PGE2is 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. PGE2and epoprostenol (a prostacyclin analog) evoked dilation of vasa recta specifically at pericyte sites, and PGE2significantly 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 PGE2was 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 PGE2concentration and may serve as the primary mechanism underlying NSAID-associated renal injury and/or further compound-associated tubular damage. |
Databáze: | OpenAIRE |
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