title: Effect on renal sodium and water excretion of the inhibition of prostaglandin synthesis in extracellular volume expansion.
abstract: In anaesthetized dogs the effect of the inhibition of prostaglandin synthesis on renal function was investigated in isosmotic extracellular volume (ECV) expansion of 1.5-2% of the body weight. The degree of ECV expansion was then elevated to about 5% of the body weight by infusing intravenously 25 ml/kg of Ringer solution within 60 minutes. Arterial blood pressure, glomerular filtration rate, CPAH, water and sodium excretion, urinary osmotic activity and Evans blue distribution space were determined in mild ECV expansion and during and after Ringer load. Prostaglandin synthesis was inhibited by giving intravenously 4 mg/kg indomethacin in ten minutes. A group of animals, receiving no indomethacin only the solvent, served as control. Indomethacin induced first a fast and afterwards a slow continuous increase in arterial blood pressure. In the control group, arterial blood pressure did not change. Glomerular filtration rate was similar in both groups throughout the whole experiment. In mild ECV expansion indomethacin decreased the PAH clearance, and renal sodium and water excretion, and elevated urinary osmotic activity as compared to the control group. During an ECV expansion of about 5% of body weight, in the control group water excretion exceeded three-fold the initial value, while sodium excretion increased only by 50% and urinary osmotic activity decreased below that of the plasma. The Evans blue distribution space increased significantly. In the indomethacin-treated animals, urine excretion increased to double the initial value, sodium excretion was similar as in the control group, and urinary osmotic activity much higher than in the control group. The Evans blue distribution space was practically unaffected by the Ringer load. In the after-load periods, the parameters investigated came nearer to each other but there was still a marked difference between the control and the indomethacin treated group at the end of the experiment. Indomethacin reduced the increase of urinary excretion under the effect of ECV expansion; control animals excreted 42.8 +/- 11.6%, while the indomethacin-treated dogs excreted only 30.2 +/- 17.6% of the water load. The alteration in renal function observed under the effect of indomethacin is attributed to functional changes in different parts of the nephron, arising probably in consequence of changes in cortical and medullary blood flow.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000502:physiology*; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D010953:Plasma Volume; D011453:Prostaglandins / Q000096:biosynthesis; D012964:Sodium / Q000502:physiology*; D010130:p-Aminohippuric Acid
chemical_list: D011453:Prostaglandins; D012964:Sodium; D007213:Indomethacin; D010130:p-Aminohippuric Acid