Diabetes insipidus in the third trimester of pregnancy.

BACKGROUND: Transient diabetes insipidus may rarely present during late pregnancy and/or the immediate puerperium, and if unrecognized, may cause neurologic injury and threaten the lives of mother and fetus. However, when recognized early and treatment is initiated with desmopressin acetate, an analog of vasopressin that is resistant to vasopressinase, water loss in the urine is eliminated and complications may be abrogated. This report aims to increase the awareness of this disorder and describes appropriate treatment. CASES: Two cases of diabetes insipidus, believed to be due to excess vasopressinase, are presented to demonstrate the clinical features, pathogenesis, and treatment of this syndrome. CONCLUSION: Awareness of the syndrome of transient diabetes insipidus may lead to early diagnosis and appropriate treatment that will reduce the risks of maternal and fetal morbidity.

Insulin-induced phosphorylation of ENaC correlates with increased sodium channel function in A6 cells.

The purpose of this study was to determine whether there is a correlation between phosphorylation and activity of the epithelial sodium channel (ENaC). The three subunits that form the channel were immunoprecipitated from A6 cells by using specific polyclonal antibodies after labeling cells with (35)S or (32)P. When immune complexes were resolved on SDS-PAGE, the alpha-subunit migrated at 85 and 65 kDa, the beta-subunit at 115 and 100 kDa, and the gamma-subunit at 90 kDa. In the resting state all three subunits were phosphorylated. The alpha-subunit was phosphorylated only in the 65-kDa band, suggesting that the posttranslational modification that gives rise to the rapidly migrating form of alpha is a requirement for phosphorylation. Stimulation with 100 nM insulin for 30 min increased phosphorylation of alpha-, beta-, and gamma-subunits approximately twofold. Exposure to 1 microM aldosterone for 16 h increased protein abundance and phosphorylation proportionately in the three subunits. When insulin was applied to cells pretreated with aldosterone, phosphorylation was also increased approximately twofold, but the total amount of phosphorylated substrate was larger than in control conditions because of the action of aldosterone. This result might explain the synergistic increase in sodium transport under the same conditions. The protein kinase C inhibitor chelerythrine abolished insulin effects and decreased sodium transport and subunit phosphorylation. Together, our findings suggest that ENaC activity is controlled by subunit phosphorylation in cells that endogenously express the channel and the machinery for hormonal stimulation of sodium transport.

Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial.

UNLABELLED: In this prospective, randomized, placebo-controlled, double-blinded study, we determined the effects of two commonly used adjuncts, mannitol and dopamine, on beta(2)-microglobulin (beta(2)M) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). beta(2)M excretion rate has been described as a sensitive marker of proximal renal tubular function. One-hundred patients with a preoperative serum creatinine level

Basolateral and apical A1 adenosine receptors mediate sodium transport in cultured renal epithelial (A6) cells.

There are conflicting reports in the literature regarding the adenosine receptor that mediates the increase in sodium transport in the A6 cell. In this study we used specific A1 and A2 adenosine receptor agonists and antagonists, as well as two different subclones of the A6 cell, to determine which adenosine receptor mediates the increase in sodium transport. In the A6S2 subclone, basolateral and apical N6-cyclohexyladenosine (CHA), a selective A1 receptor agonist, stimulated sodium transport at a threshold concentration <10(-7) M, whereas CGS-21680, a selective A2 receptor agonist, had a threshold concentration that was at least 10(-5) M. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was found to have a nonspecific effect on CHA-stimulated sodium transport, whereas the A2 receptor antagonist 8-(3-chlorostyryl)caffeine (CSC) had no effect. As with the A6S2 subclone, basolateral and apical CHA stimulated sodium transport at a nanomolar concentration in the A6C1 subclone and the threshold concentration for CGS-21680 was in the high micromolar range. Concurrent with the increase in 1 receptor in different subclones of the A6 cell, including a subclone capable of anion secretion.

On the natriuretic effect of verapamil: inhibition of ENaC and transepithelial sodium transport.

The natriuretic effect of Ca(2+) channel blockers has been attributed to hemodynamic changes and to poorly defined direct tubular effects. To test the possibility that verapamil may inhibit Na(+) reabsorption at the distal tubule, its effect on transepithelial Na(+) transport in aldosterone-stimulated A6 cells was determined. Cells were grown on permeable supports, and short-circuit current (I(sc)) measured in an Ussing chamber was used as a surrogate marker for transepithelial Na(+) transport. Application of 300 microM verapamil to the apical side inhibited I(sc) by 77% and was nearly as potent as 100 microM amiloride, which inhibited I(sc) by 87%. Verapamil-induced inhibition of I(sc) was accompanied by a significant increase in transepithelial resistance, suggesting blockade of an apical conductance. Its action on transepithelial Na(+) transport does not appear to occur through inhibition of L-type Ca(2+) channels, since I(sc) was unaffected by removal of extracellular Ca(2+). Verapamil also does not appear to inhibit I(sc) by modulating intracellular Ca(2+) stores, since it fails to inhibit transepithelial Na(+) transport when added to the basolateral side. The effect on Na(+) transport is specific for verapamil, since nifedipine, Ba(2+), 4-aminopyridine, and charybdotoxin do not significantly affect I(sc). A direct effect of verapamil on the epithelial Na(+) channel (ENaC) was tested using oocytes injected with the alpha-, beta-, and gamma-subunits. We conclude that verapamil inhibits transepithelial Na(+) transport in A6 cells by blocking ENaC and that the natriuresis observed with administration of verapamil may be due in part to its action on ENaC.