Differential renal effects of cyclooxygenase inhibition in sodium-replete and sodium-deprived dog.
We studied the renal effects of the cyclooxygenase inhibitor sodium meclofenamate (M) (5 mg/kg, iv) in the pentobarbital-anesthetized dog that had been maintained on an elevated (100 meq/day) or on a reduced (< meq/day) sodium intake, and during the administration of antiotensin II in the sodium-replete dog, or the angiotensin receptor blocker [Sar1-Ala8]angiotensin II in the sodium-deprived dog. In the sodium-replete dog, M did not affect mean arterial blood pressure (MABP), renal blood flow (RBF), glomerular filtration rate, (GFR), or urine volume (V), but reduced the urinary excretion of sodium (UNaV) by 47%, and of immunoreactive PGE2 (iPGE2) by 90%. However, in the sodium-replete dog during angiotensin II infusion (3 ng . kg-1 . min-1, iv), M reduced RBF by 35%, GFR by 24%, V by 72%, and iPGE2 by 94%. Similarly, in the sodium-deprived dog M reduced RBF by 34%, GFR by 28%, and iPGE2 excretion by 89%. However, M did not affect RBF or GFR in the sodium-deprived dog during infusion of [Sar1-Ala8]angiotensin II (6 microgram . kg-1 . min-1, iv), although iPGE2 excretion was reduced by 84%. This study demonstrates that the effects of M on renal hemodynamics in the dog vary with the state of sodium balance and suggests that a prostaglandin(s) contributes to maintenance of renal blood flow during activation of the renin-angiotensin system.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism*
D000804:Angiotensin II; D008469:Meclofenamic Acid; D012964:Sodium; D012083:Renin