Inhibition of prostaglandin synthesis and the action of vasopressin during extracellular volume expansion in the dog.
The increased renal sodium and water excretion after an intravenous infusion of Ringer solution has been investigated in anaesthetized dogs. The response of the kidneys has been examined in four combinations. The functional parameters of renal function have been compared during volume expansion by 1.5-2.0% body weight Ringer solution and overhydration by 2.5% Ringer solution for 60 min. In the control animals, volume expansion by 2% body weight Ringer solution resulted in a significant increase in sodium excretion and urine flow. When these animals were infused with 2.5% body weight Ringer solution a marked increase in water excretion was observed with a smaller increment in sodium excretion, and the urine became hypo-osmotic as compared to the plasma. No difference was found in glomerular filtration rate and PAH clearance. In the group No. 2, the effect of 4 mg/kg indomethacin infusion was studied. The inhibition of prostaglandin synthesis considerably reduced the diuretic effect of Ringer infusion and did not affect sodium excretion. In the group No. 3, the animals received lysine-8-vasopressin i.v. in a preliminary dose of 10 mU/kg during 10 min and then 50 mU/kg over 60 min in infusion. Volume expansion with 2.5% body weight of Ringer solution resulted in a marked increase in sodium and water excretion but no difference was found in glomerular filtration rate and PAH clearance. Dilution of the urine i.e. a decrease of urinary osmolarity, in spite of the vasopressin infusion, was significantly higher in this group than in the control animals (group No. 1). In the fourth series, after 4 mg/kg of indomethacin the same dose of vasopressin was administered as in group No. 3. Indomethacin was observed to inhibit the diuretic effect of vasopressin and did not affect the saluretic effect. From these data it was concluded that medullary tonicity affected renal water handling during extracellular isosmotic hypervolaemia induced by Ringer infusion. This mechanism depends on medullary prostaglandin synthesis and is independent from the plasma vasopressin concentration. Our findings clearly indicate that extracellular hypervolaemia increases renal sodium excretion and lysine-8-vasopressin was found to potentiate this effect. This sodium excretion increasing mechanism does not depend on renal prostaglandin secretion, nor were glomerular factors responsible for the increase of sodium and water excretion.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism*; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D011453:Prostaglandins / Q000096:biosynthesis*; D012964:Sodium / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*
D011453:Prostaglandins; D014667:Vasopressins; D012964:Sodium; D007213:Indomethacin