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 studied. Experiments were performed in rats with chronic (8 weeks) inhibition of NO (NG-nitro L-arginine methyl Ester, L-NAME, 40 mg/kg/day) with or without simultaneous PGs synthesis blockade (indomethacin, 1 mg/kg/day). A time control group with no treatment was studied in parallel. At the end of this period, the animals were anesthetized and renal hemodynamics and excretion were studied at three levels of renal perfusion pressure (RPP; 100, 125 and 150 mm Hg). Renal blood flow, glomerular filtration rate, diuresis and natriuresis were lower at the three RPP levels in both L-NAME-treated groups than in the control or indomethacin-treated animals. Simultaneous administration of indomethacin plus L-NAME did not further modify the hemodynamic or excretory responses observed in the L-NAME-treated animals. These results show that chronic NO inhibition impairs the renal excretory response to changes in renal perfusion pressure, and simultaneous NO and prostaglandin synthesis inhibition does not reduce those responses further. It is concluded that, on a long-term basis, a preserved NO production, but not prostaglandin production, is critical for a normal pressure diuretic and natriuretic mechanism.