Effect of indomethacin on renal function during different levels of surgical stress

To determine whether renal prostaglandins participate in the regulation of renal blood flow, sodium and water excretion during "stress situation", renal function was investigated in two groups of anaesthetized dogs, subjected to minor and to more severe surgical stress under control conditions, and following the administration of 4 mg/kg indomethacin i.v. In the control studies, the renal haemodynamic parameters (CPAH, Cinulin), urine output and sodium excretion were not different in those animals in which the surgical traumatization was more severe from data obtained in similarly anaesthetized dogs. Extracellular volume expansion induced with i.v. infusion of Ringer solution enhanced sodium and water excretion in both groups, however, the increase of sodium excretion was less in the dogs subjected to more severe stress. During indomethacin infusion glomerular filtration did not change in either groups; CPAH decreased by 20-25% in the anaesthetized animals and 35-40% in dogs in which the surgical stress was more severe. In this group the total renal blood flow was reduced by 40% simultaneously with the haemodynamic changes; sodium and water excretion fell in both groups. After indomethacin infusion the diuretic response of the kidneys to extracellular volume expansion was markedly reduced in the anaesthetized dogs, the diuretic and natriuretic effects being almost completely inhibited in the animals subjected to more severe stress. These data suggest that in the anaesthetized dog endogenous prostaglandins may serve to maintain renal blood flow but not the glomerular filtration rate. Inhibition of prostaglandin synthesis during more severe stress results in increased renal vascular resistance and reduced renal blood flow. Accordingly, the data provide evidence that renal prostaglandins counteract in the kidney the vasoconstrictor mechanisms activated during more severe surgical traumatization. The data do not support the direct physiological role of prostaglandins in regulating tubular function.