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

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-wk-clipping the left renal artery of canine kidneys, and renal interstitial nitrate+nitrite and PGE(2) 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%). N(omega)-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 PGE(2) 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 PGE(2) 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.

• Authors: Hirobumi Tokuyama, Koichi Hayashi, Hiroto Matsuda, Eiji Kubota, Masanori Honda, Ken Okubo, Yuri Ozawa, Takao Saruta
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 282 Issue 5 Pg. F859-65 (May 2002) ISSN: 1931-857X [Print] United States
• PMID: 11934696 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Enzyme Inhibitors
• Nitrates
• Nitrites
• Prostaglandins
• Nitric Oxide
• Dipyrone
• Nitric Oxide Synthase
• Dinoprostone
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Blood Flow Velocity
• Chronic Disease
• Dinoprostone (analysis)
• Dipyrone (pharmacology)
• Dogs
• Enzyme Inhibitors (pharmacology)
• Glomerular Filtration Rate
• Hemodynamics
• Ischemia (physiopathology)
• Kidney (blood supply)
• Male
• Microdialysis
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitrates (analysis)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitrites (analysis)
• Prostaglandins (physiology)
• Renal Artery (surgery)
• Renal Artery Obstruction (physiopathology)