Renal function and tubular transport effects of sulindac and naproxen in chronic heart failure.
Renal function and excretion of water, salt, and the prostacyclin hydration product (6-keto-PGF1 alpha) were evaluated in 10 furosemide-treated patients with well-controlled congestive heart failure. Four doses of sulindac (200 mg b.i.d.) and naproxen (500 mg b.i.d.) were given every 12 hours in a double-blind crossover design. Naproxen significantly decreased the urinary excretion of water (19%), sodium (26%), chloride (26%), and 6-keto PGF1 alpha (76%) and decreased osmolal clearance (18%). No significant changes in these functions were observed in the patients receiving sulindac. Plasma renin activity, plasma aldosterone, freewater clearance, or clearance of furosemide did not change significantly with either treatment. Although the basal glomerular filtration rate (GFR) and renal plasma flow (RPF) were reduced, these patients with cardiac disease, with normal serum sodium concentration, did not have any further reduction of GFR or RPF despite naproxen-induced inhibition of renal prostacyclin synthesis. It is concluded that renal prostaglandins contribute to the natriuretic effect of oral furosemide in patients with compensated congestive heart failure. In this clinical setting, GFR and RPF are not critically dependent on intact renal PGI2 synthesis. The lack of effect on renal prostaglandin synthesis and the renal response to oral furosemide supports the concept of a renal sparing effect of sulindac.
Eriksson
L O
LO
Department of Clinical Pharmacology, University Hospital, Lund, Sweden.
Beermann
B
B
Kallner
M
M
D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D002908:Chronic Disease; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D009288:Naproxen / Q000378:metabolism / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D013467:Sulindac / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*
D004573:Electrolytes; D007192:Indenes; D011453:Prostaglandins; D013467:Sulindac; D009288:Naproxen; C025462:sulindac sulfide; D005665:Furosemide; D012083:Renin