Stenosis-dependent role of nitric oxide and prostaglandins in chronic renal ischemia

Hirobumi Tokuyama, Koichi Hayashi, Hiroto Matsuda, Eiji Kubota, Masanori Honda, Ken Okubo, Yuri Ozawa, Takao Saruta

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Abstract

The role of nitric oxide (NO) and prostaglandins (PG) in modifying renal hemodynamics was examined in clipped and nonclipped kidneys of unilateral renal artery stenosis. Chronic unilateral renal ischemia was established by 4-wkclipping the left renal artery of canine kidneys, and renal interstitial nitrate+nitrite and PGE2 contents were evaluated by the microdialysis technique. Unilateral renal artery stenosis caused 45 ± 1 and 73 ± 1% decrements in renal plasma flow (RPF) in moderately and severely clipped kidneys and 21 ± 3% decrements in nonclipped kidneys with severe stenosis. Renal nitrate+nitrite decreased in moderately (-31 ± 1%) and severely clipped kidneys (-63 ± 4%). Nω-nitro-L-arginine methyl ester reduced RPF (-56 ± 3%) and glomerular filtration rate (GFR; -54 ± 3%) in moderately clipped kidneys, whereas this inhibitory effect was abolished in severely clipped kidneys. In contrast, renal PGE2 contents increased modestly in moderate clipping and were markedly elevated in severely clipped kidneys (from 111 ± 7 to 377 ± 22 pg/ml); sulpyrine impaired renal hemodynamics only in severely clipped kidneys. In contralateral nonclipped kidneys, although renal PGE2 was not increased, sulpyrine reduced RPF (-32 ± 1%) and GFR (-33 ± 3%) in severe stenosis. Collectively, NO plays a substantial role in maintaining renal hemodynamics both under basal condition and in moderate renal artery stenosis, whereas the contributory role shifts from NO to PG as renal artery stenosis progresses. Furthermore, because intrarenal angiotensin II is reported to increase in nonclipped kidneys, unilateral severe ischemia may render the nonclipped kidney susceptible to PG inhibition.

Original languageEnglish
Pages (from-to)F859-F865
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number5 51-5
Publication statusPublished - 2002 Jun 29

Keywords

  • Ischemic nephropathy
  • Renal artery stenosis
  • Renal hemodynamics

ASJC Scopus subject areas

  • Physiology
  • Urology

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    Tokuyama, H., Hayashi, K., Matsuda, H., Kubota, E., Honda, M., Okubo, K., Ozawa, Y., & Saruta, T. (2002). Stenosis-dependent role of nitric oxide and prostaglandins in chronic renal ischemia. American Journal of Physiology - Renal Physiology, 282(5 51-5), F859-F865.