Zambraski E J, Guidotti S M, Atkinson D C, Diamond J
Department of Biology--Physiology Section, Rutgers University, New Brunswick, New Jersey.
J Pharmacol Exp Ther. 1988 Dec;247(3):983-8.
In patients with liver disease, or in normal subjects who are sodium-depleted, the administration of either a nonsteroidal anti-inflammatory drug or acetylsalicylate (aspirin) has a detrimental effect on the kidney; profound renal vasoconstriction and the retention of sodium and water may occur. We observed recently that salicylate (SA), in contrast to meclofenamate (MECLO) or aspirin, caused a diuresis and natriuresis in the sodium-depleted dog. To determine if SA would similarly affect the kidneys in a cirrhotic subject, the effects of SA (40 mg/kg) and subsequent MECLO treatment (2 mg/kg) were evaluated in five normal and six common bile-duct-ligated (CBDL) miniature swine. All six CBDL animals showed signs of biliary cirrhosis and four of the six were ascitic at the time of study. SA did not significantly alter renal blood flow or glomerular filtration rate in either the normal or CBDL animals. In both groups, SA caused a significant diuresis and natriuresis. MECLO, given after SA, caused a reduction in renal blood flow in the normal but not in the CBDL animals, but did not alter glomerular filtration rate in either group. In the CBDL animals, when MECLO was given alone a significant decrease in renal blood flow occurred. MECLO abolished the SA-induced diuresis and natriuresis in the normal swine but only affected the SA-mediated natriuresis in the CBDL animals. SA significantly reduced renal prostaglandin E2 excretion in both groups. With MECLO, prostaglandin E2 excretion was reduced further in the normals but not in the CBDL animals. These data demonstrate that SA does not produce detectable renal vasoconstriction in the cirrhotic pig.(ABSTRACT TRUNCATED AT 250 WORDS)
