dinoprost and Hypokalemia

In 2 adult patients with Bartter's syndrome, in whom chloride reabsorption at the diluting segment of the nephron was markedly reduced, serum potassium concentration could be improved with oral administration of a large amount of potassium chloride. In both cases, improvement of serum potassium levels with oral potassium load resulted in an increase in plasma renin activity (PRA) and plasma aldosterone concentration (PAC), a decrease in urinary excretion of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), and an improvement of pressor responsiveness to angiotensin II and norepinephrine. Treatment with indomethacin also improved the pressor responsiveness to angiotensin II and norepinephrine, but this occurred in association with a decrease in PRA, PAC and urinary excretion of PGE2 and PGF2 alpha. These results indicated that an event at the renal tubular level leading to potassium depletion is the most proximal pathogenetic defect in Bartter's syndrome, and that this in turn contributes to excessive prostaglandin production leading further to the decreased pressor responsiveness to vasoactive substances.

Topics: Aldosterone; Angiotensin II; Bartter Syndrome; Blood Pressure; Dinoprost; Dinoprostone; Female; Humans; Hyperaldosteronism; Hypokalemia; Indomethacin; Male; Middle Aged; Norepinephrine; Potassium; Potassium Chloride; Prostaglandins E; Prostaglandins F; Renin

1. To examine the hypothesis that the normalcy of blood pressure, despite an increase in circulating angiotensin II, and the blood pressor hyporesponsiveness to infusion of pressor agents which are associated with hypokalaemia, are due to overproduction of prostacyclin, the principal prostaglandin (PG) synthesized by the vascular endothelium, we studied the effect of experimental hypokalaemia on the urinary excretion of immunoreactive 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, in the rat. 2. The animals were fed on a potassium-deficient diet for 9 days. Twenty-four hour urine samples were collected daily for measurement of urinary excretion of immunoreactive 6-keto-PGF1 alpha, PGE2 and 13,14-dihydro-15-keto-PGF2 alpha (PGFM). 3. Hypokalaemia caused significant increases of the three prostaglandins measured. 4. We conclude that hypokalaemia is a potent stimulus of both renal and vascular prostaglandins. The results suggest that an increase in prostacyclin synthesis in peripheral blood vessel walls may be responsible for the resistance of blood pressure to infusion of pressor substances as well as for the normalcy of blood pressure, despite the presence of high circulating angiotensin II concentrations, in conditions associated with hypokalaemia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Creatinine; Dinoprost; Dinoprostone; Epoprostenol; Hypokalemia; Potassium; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Renin; Sodium