Hypokalaemia Stimulates Prostacyclin Synthesis in the Rat

Abstract

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.

PGE2 inhibits apical K channels in the CCD through activation of the MAPK pathway

“…However, the effect of K intake on renal PGE 2 levels is varied: low-K intake for 3 wk has been shown to decrease urinary PGE 2 excretion in rabbit kidney (2) while the K restriction for 9 days has been reported to increase urinary PGE 2 excretion in the rat kidney (17). Thus the effect of K restriction on PGE 2 synthesis depends on the animal species and duration of K depletion.…”

“…Because activation of MAPK has been shown to inhibit both ROMK and big-conductance K (BK) channels (3,26), it is expected that stimulation of EP1 receptor should inhibit ROMK and BK channels in the CCD. Furthermore, dietary K intake has been shown to affect PGE 2 production (2,17). Thus it is possible that PGE 2 may play a role in mediating the effect of K restriction on apical K channels in the CCD.…”

Dehydration-induced increase in aquaporin-2 protein abundance is blocked by nonsteroidal anti-inflammatory drugs

“…This study aimed to address the first of these questions. Because prostaglandins have been reported to be increased after vasopressin treatment (35), and in various acquired forms of NDI (14,33,36), and because NSAIDs are sometimes used in the management of NDI (18), our initial hypothesis was that increased prostaglandin synthesis might decrease AQP2 expression, and so we predicted that NSAID treatment might increase AQP2 levels. Our results are clearly not consistent with this hypothesis, since 1) we see a decrease in AQP2 levels after NSAID treatment, and 2) we do not see a significant decrease in PGE levels after NSAID treatment, suggesting that the effect on AQP2 levels may be mediated by some other effect of these drugs.…”

Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.

“…While hypokalemia has been associated with increased prostaglandin production (13)(14)(15), and inhibitors of prostaglandin synthesis restore the responsiveness of rabbit isolated perfused collecting ducts to vasopressin (14), prostaglandins do not appear to be an important factor in the etiology of hypokalemia-induced polyuria in rats (16). In the rat, there may be a decrease in adenylate cyclase sensitivity in response to vasopressin (2,17), thus reducing production of cAMP, the second messenger for vasopressin action.…”