Influence of renal sympathectomy, sodium depletion and prostaglandin synthetase inhibition on prostaglandin production and [3H]PGE2 binding characteristics in rat kidney.
The effects of renal sympathectomy (unilateral, renal microsurgical denervation), sodium depletion (hypovolaemia) and prostaglandin synthetase inhibition on the rate of prostaglandin synthesis and [3H]PGE2 binding characteristics were studied in the rat kidney. The intrarenal rate of prostaglandin synthesis was measured by monitoring the urinary excretion of 6-keto-PGF1 alpha, the stable hydration product of prostacyclin. Dietary sodium restriction was associated with a 99% decrease in urinary sodium excretion (P less than 0.001) and a 17% decrease of urine volume (n.s.). Renal denervation or sodium deprivation changed neither the rate of excretion of 6-keto-PGF1 alpha nor the density or affinity of [3H]PGE2 binding sites as compared to control. However, in sodium-depleted rats, prostaglandin synthesis inhibition, induced by naproxen, decreased the urinary excretion of 6-keto-PGF1 alpha by 40% (P = 0.011) and increased the number of [3H]PGE2 binding sites by almost 30% (P = 0.031) with no change in binding affinities as compared with sodium-depleted controls. In contrast, sulindac was not able to suppress the renal synthesis and excretion of 6-keto-PGF1 alpha, and did not modulate the [3H]PGE2 binding characteristics. The lack of effect on the excretion of 6-keto-PGF1 alpha and on the [3H]PGE2 binding characteristics supports the view that sulindac spares renal prostaglandin synthesis.
Eriksson
L O
LO
Department of Clinical Pharmacology, University Hospital, Lund, Sweden.
Larsson
B
B
Kullendorff
C M
CM
Andersson
K E
KE
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D003714:Denervation; D015232:Dinoprostone / Q000378:metabolism*; D007668:Kidney / Q000294:innervation / Q000378:metabolism / Q000601:surgery*; D008297:Male; D009288:Naproxen / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000172:deficiency / Q000378:metabolism*; D013467:Sulindac / Q000494:pharmacology; D013562:Sympathectomy; D014316:Tritium
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D014316:Tritium; D013467:Sulindac; D009288:Naproxen; D012964:Sodium; D015232:Dinoprostone