6-ketoprostaglandin-f1-alpha and Hypokalemia

Plasma renin activity (PRA) and urinary aldosterone excretion were determined in healthy women with normal potassium balance (N, n = 20) or experimental potassium depletion (KD). KD was induced by natriuretic treatment--associated with replacement of net NaCl and water losses--and low dietary potassium intake (< or = 10 mmol/d). By using different depletion patterns, three groups were obtained with cumulative potassium deficits (mean +/- SEM) of 160 +/- 43 (KD1, n = 8), 198 +/- 22 (KD2, n = 6) and 215 +/- 54 mmol (KD3, n = 6). The renal function by the clearance (cl.) method and urinary concentrations of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha (6KPGF), and thromboxane B2 (TXB2) by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by low-dose infusion of lysine-8-vasopressin (LVP). 1. In all KD groups the depletion treatment significantly reduced both potassium plasma concentration (PK) and urinary potassium excretion while it increased basal PRA; the basal urinary aldosterone excretion was not significantly different from normokalemic controls. In the KD3 vs KD1 group the P kappa value was significantly lower. 2. In both KD2 and KD3 groups as compared to the N group, several hypokalemic-like renal dysfunctions--absent in the KD1 group--occurred. Particularly, in the KD2 + KD3 vs N group the renal ability in both urine diluting (water load) and concentrating (LVP infusion) was significantly impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aldosterone; Blood Pressure; Dinoprostone; Diuresis; Female; Glomerular Filtration Rate; Humans; Hypokalemia; Kidney; Middle Aged; Natriuresis; Polyuria; Potassium; Potassium, Dietary; Prostaglandins; Renin; Renin-Angiotensin System; Thromboxane B2

In hyperprostaglandin E syndrome (HPGES) and classic Bartter syndrome (cBS), tubular salt and water losses stimulate renin secretion, which is dependent on enhanced cyclooxygenase-2 (COX-2) enzymatic activity. In contrast to other renal COX metabolites, only prostaglandin E(2) (PGE(2)) is selectively up-regulated in these patients. To determine the intrarenal source of PGE(2) synthesis, we analyzed the expression of microsomal PGE(2) synthase (mPGES; EC: 5.3.99.3), whose product PGE(2) has been shown to stimulate renin secretion in vitro. Expression of mPGES was analyzed by immunohistochemistry in eight patients with HPGES, in two patients with cBS, and in six control subjects. Expression of mPGES immunoreactive protein was observed in cells of the macula densa in five of eight HPGES patients and in one of two cBS patients. Expression of mPGES immunoreactive protein was not observed in cells associated with the macula densa in kidneys from control subjects without a history consistent with activation of the renin angiotensin system. Co-induction of COX-2 and mPGES in cells of the macula densa suggests that PGE(2) activates renin secretion in humans.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Antibody Specificity; Child; Child, Preschool; Cyclooxygenase 2; Dinoprostone; Female; Humans; Hypokalemia; Immunohistochemistry; Intramolecular Oxidoreductases; Isoenzymes; Juxtaglomerular Apparatus; Kidney Diseases; Kidney Tubules; Male; Membrane Proteins; Microsomes; Prostaglandin-E Synthases; Prostaglandin-Endoperoxide Synthases; Renin; Salts; Signal Transduction

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

We measured plasma levels of 6-keto-prostaglandin F1 alpha by radioimmunoassay in patients with hypokalemia due to various disorders. Plasma 6-keto-PGF1 alpha in patients with disorders involving hypokalemia was not different from that of normal controls. Treatment with inhibitors of prostaglandin synthesis for 5-7 days in three patients with Bartter's syndrome decreased 6-keto-PGF1 alpha plasma levels by about 25%. It is suggested that, plasma 6-keto-PGF1 alpha may, on occasions, be a poor index of circulating prostacyclin.

Topics: 6-Ketoprostaglandin F1 alpha; Bartter Syndrome; Cathartics; Female; Humans; Hypokalemia; Substance-Related Disorders; Vomiting