CHRONIC EFFECTS OF NITRIC-OXIDE AND PROSTAGLANDIN INHIBITION ON PRESSURE DIURESIS AND NATRIURESIS IN RATS

The long-term interaction between nitric oxide (NO) and prostaglandins (PGs) in the pressure diuresis and natriuresis response has been stud ied. Experiments were performed in rats with chronic (8 weeks) inhibit ion of NO (N-G-nitro L-arginine methyl Ester, L-NAME, 40 mg/kg/day) wi th or without simultaneous PGs synthesis blockade (indomethacin, 1 mg/ kg/day). A time control group with no treatment was studied in paralle l. At the end of this period, the animals were anesthetized and renal hemodynamics and excretion were studied at three levels of renal perfu sion pressure (RPP; 100, 125 and 150 mm Hg). Renal blood flow, glomeru lar filtration rate, diuresis and natriuresis were lower at the three RPP levels in both L-NAME-treated groups than in the control or indome thacin-treated animals. Simultaneous administration of indomethacin pl us L-NAME did not further modify the hemodynamic or excretory response s observed in the L-NAME-treated animals. These results show that chro nic NO inhibition impairs the renal excretory response to changes in r enal perfusion pressure, and simultaneous NO and prostaglandin synthes is inhibition does not reduce those responses further. It is concluded that, on a long-term basis, a preserved NO production, but not prosta glandin production, is critical for a normal pressure diuretic and nat riuretic mechanism.