Indomethacin and diclofenac sodium increase sodium and water excretion after extracellular volume expansion in the rabbit.
The renal effects of an acute extracellular fluid volume expansion (50 ml Ringer/kg body weight/60 min) were studied in aldosterone-treated (100 microgram/kg), anesthetized rabbits with and without pretreatment with either indomethacin (3.0 mg/kg) or diclofenac sodium (3.0 mg/kg), two different inhibitors of renal prostaglandin (PG) biosynthesis. In controls (n = 7), the volume expansion increased urine flow from 1.5 +/- 0.24 to 6.1 +/- 0.5 (S.E.) ml/min/100 g kidney weight and sodium excretion from 0.15 +/- 0.03 to 0.99 +/- 0.10 mmol/min/100 g. PAH and inulin clearance increased by 42 and 58%, respectively, while plasma renin activity and urinary excretion of PGF2 alpha-like immunoreactivity were reduced (P less than 0.05). In animals pretreated with indomethacin (n = 6) or diclofenac sodium (n = 6), the diuresis and the natriuresis following volume expansion were significantly increased about two-fold over controls, whereas PAH and inulin clearance, plasma renin activity and hematocrit did not differ from controls. Both drugs were found to reduce urinary excretion of PGF2 alpha-like immunoreactivity by 75--95% througout the experiment. The results indicate that diclofenac sodium, indomethacin and extracellular volume expansion enhance sodium and water excretion partly by suppression of a PG sensitive reabsorption process in the kidney.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000187:drug effects / Q000378:metabolism*; D004008:Diclofenac / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism*; D006400:Hematocrit; D007213:Indomethacin / Q000494:pharmacology*; D007444:Inulin; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D011453:Prostaglandins / Q000652:urine; D011817:Rabbits; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine*; D013997:Time Factors; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D010648:Phenylacetates; D011453:Prostaglandins; D004008:Diclofenac; D007444:Inulin; D012964:Sodium; D012083:Renin; D007213:Indomethacin; D010130:p-Aminohippuric Acid