The objective of this study was to evaluate the effects of oral protein load on the glomerular and tubulointerstitial functions, considering the roles of renal prostaglandin and angiotensin II (AII), by means of pharmacological inhibition of the mechanisms involved. Seven intact healthy dogs (3 males and 4 females) were enrolled. They were medium-sized, adult, multi-mixed-breed dogs. All of them were adapted to the experimental management. Three consecutive pairs of experiments were conducted at 7-day intervals. The first pair included a baseline assessment (control) and oral protein load (OPL) consisting of powdered egg white at 4.7 g/kg of body weight (partially rehydrated fo consumption). For the second pair, the dogs were treated with flunixin meglumine, a nonsteroidal anti-inflammatory drug (NSAID), at 1.1 mg/kg, q 12 h, for two days, and OPL on the second day (NSAID + OPL). For the third pair of experiments, the dogs were treated with enalapril maleate, an angiotensin-converting-enzyme inhibitor (ACEi), at 0.5 mg/kg, q 12 h and OPL on the second day (ACEi + OPL). Endogenous creatinine clearance (eCcr), urine protein-to-creatinine ratio (UP/C), urine output (UOP), sodium fractional excretion (NaFE), and serum and urine osmolaliy (sOsm; uOsm) were obtained during a 4 hours period of urine collection, after overnight 12 hours fasting followed by OPL when indicated. Water ad libitum was available during fasting and evaluation. Oral protein load increased (P < .05) glomerular filtration rate (GFR), even when subjects were under the effect of NSAID or ACEi, although, at a lower rate (P < .05). Urine output and NaFE increased (P < .05) as well, even under the ACEi effect. With NSAID the GFR did not change significantly, suggesting that prostanoids would not participate in the regulatory mechanism of glomerular filtration. However, renal hydrosaline regulation was modified, although OPL addition was effective in inducing a different response. The increase of GFR following ACEi inhibition evidenced a possible role of AII in maintaining a low GFR during fasting as observed in the baseline control. The association with the OPL, unexpectedly, resulted in a statistically non-significant increase in UP/C (range 0.1 to 0.4), that reached a pathological level, although the GFR increase was lower (P = .015) than obtained previously (only ACEi). The study presented, despite having a small n, raises a possible basis for further investigations that may explain and confirm the benefits of protein restrictions in CKD.