Renal effects of endogenous prostaglandin synthesis promoter ONO-3122.
The renal effects of a prostaglandin synthesis agonist, 1-iodo-3-aminomethyl-5,6,7,8-tetrahydro-2-naphthol (ONO-3122), were investigated in anesthetized rats. ONO-3122 (0.3 mg/kg + 0.3 mg.kg-1.h-1 iv) doubled the urinary excretion of the main metabolites of prostaglandin F, and induced transient increases in renal blood flow and glomerular filtration rate (GFR) with a marked, stable natriuresis. Indomethacin suppressed the natriuresis. When the diuretic fluid losses were replaced, micropuncture showed an unaltered reabsorption of sodium in the proximal tubule but reductions in the loop of Henle (86 +/- 1 vs. 76 +/- 1%) and in the more distal segments (98 +/- 1 vs. 83 +/- 3%) with comparable reductions in water reabsorption. Potassium secretion was seen in the distal and collecting tubules. Without fluid replacement, sodium reabsorption was reduced in the loop and more distal nephron but increased in the proximal tubule. Differences between proximal and distal nephron GFR were unaffected by systemic ONO-3122. Loop perfusion with ONO-3122 did not change tubuloglomerular feedback responses, which were, however, completely suppressed by furosemide. It is concluded that ONO-3122 stimulates renal prostaglandin biosynthesis, transiently dilates renal vasculature, and induces natriuresis mainly by suppressing sodium and water reabsorption in the loop of Henle and the more distal nephron. Luminal ONO-3122 does not affect the tubuloglomerular feedback.
Takabatake
T
T
First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Hara
H
H
Ishida
Y
Y
Ohta
H
H
Kobayashi
K
K
D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009284:Naphthols / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D011453:Prostaglandins / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000652:urine; D011677:Punctures; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D009284:Naphthols; D011453:Prostaglandins; D011460:Prostaglandins F; C035374:1-iodo-3-aminomethyl-5,6,7,8-tetrahydro-2-naphthol