AJP - Renal Physiology, Vol 262, Issue 6 1047-F1054, Copyright © 1992 by American Physiological Society
Renal effects of endogenous prostaglandin synthesis promoter ONO-3122
T. Takabatake, H. Hara, Y. Ishida, H. Ohta and K. Kobayashi
First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
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.
