Effects of salicylate vs. aspirin on renal prostaglandins and function in normal and sodium-depleted dogs.
The effects of aspirin (acetylsalicylate) (ASA) and nonsteroidal antiinflammatory drugs (NSAIDs) on renal prostaglandin (PG) biosynthesis and function have been studied extensively. In contrast, the in vivo effects of a nonacetylated salicylate (SA), such as sodium SA, on renal function have not been well characterized. No studies have examined the effects of SA on renal function in a situation in which the maintenance of normal kidney function is dependent upon intact renal PG synthesis (i.e., sodium restriction-elevated plasma renin activity). To evaluate the effects of SA vs ASA and/or a NSAID, normal and sodium-restricted anesthetized dogs were treated with SA and then meclofenamate (MECLO) or ASA followed by MECLO. In the normal animals, SA significantly decreased renal PGE2 and PGF2 alpha excretion. After SA a significant amount of MECLO-suppressible PGE2 and PGF2 alpha synthesis remained intact. Compared to SA, with ASA there was a greater decrease in PG excretion, with no further decrease in PG excretion with subsequent MECLO treatment. In the sodium-restricted animals (plasma renin activity, 18-24 ng of angiotensin l/ml/hr) ASA decreased PGE2 excretion but SA did not. In these animals SA did not cause renal vasoconstriction. Additional groups of sodium-restricted animals were studied with extremely high doses of ASA and SA (90 mg/kg) to elevate plasma SA to 200 to 250 micrograms/ml. In these animals SA did decrease PGE2 excretion significantly, but only to levels seen typically in normal animals and, after SA, a large amount of PGE2 excretion could be suppressed by MECLO.(ABSTRACT TRUNCATED AT 250 WORDS)
Zambraski
E J
EJ
Department of Biology, Rutgers University, New Brunswick, New Jersey.
Atkinson
D C
DC
Diamond
J
J
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid
D011453:Prostaglandins; D012459:Salicylates; D008469:Meclofenamic Acid; D020156:Salicylic Acid; D001241:Aspirin; D011188:Potassium