Effect of leukotrienes of renal water excretion.
To investigate the renal actions of leukotrienes (LT), we infused arachidonic acid into the renal artery of anesthetized dogs during systemic cyclooxygenase inhibition (with ibuprofen) alone or in combination with lipoxygenase inhibition or LTD4/LTE4 receptor antagonism. Renal arachidonic acid infusion following ibuprofen alone decreased urine osmolality (945 +/- 143 to 698 +/- 144 mosm/kg; p < 0.01) and increased urine flow rate (0.34 +/- 0.11 to 0.56 +/- 0.16; p < 0.05) without altering renal blood flow, glomerular filtration rate or sodium excretion. In separate groups, prior inhibition of lipoxygenase (propylgallate) or blockade of LTD4/LTE4 receptors (LY171883) prevented the changes in urine osmolality and urine flow rate. Intrarenal oleic acid infusion following ibuprofen had no effect on renal function. Analysis of the renal papillae at the end of the experiment indicated that interstitial osmolality and sodium, potassium and urea contents were the same in all groups, ruling out a decrease in papillary interstitial osmolality as the cause of the decrease in urine osmolality in the arachidonic acid-infused group. Our experiments suggest that renal LT can decrease urine osmolality and increase urine flow rate and may play a role in renal water excretion.
Department of Cardiovascular and Metabolic Disorders, Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
D A
DA
Hartupee
J C
JC
Passmore
A
A
Jimenez
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D007052:Ibuprofen / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D017999:Leukotriene E4; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009994:Osmolar Concentration; D011435:Propyl Gallate / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014556:Urine / Q000502:physiology*
D000098:Acetophenones; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; D013777:Tetrazoles; D016718:Arachidonic Acid; D017999:Leukotriene E4; C044660:LY 171883; D011435:Propyl Gallate; D007052:Ibuprofen