The pathogenesis of peripheral cardiac edema.
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Boiled homogenates of kidneys from volume-expanded and hydropenic rats were subjected to column chromatography. The fraction eluting within the range of partition coefficients (Kav) 0.76-0.89 (fraction III) was lyophilized and the effects of this semipurified preparation were assessed on short-circuit current (SCC) across isolated frog skin, on rat kidney cortex Na-K-ATPase activity, and on sodium excretion by the rat in vivo. At a dose of 500 mug/ml, fraction III from expanded rat kidney inhibited SCC by 21 +/- 5% (P less than 0.01), whereas the same fraction from hydropenic rat kidney produced an insignificant change in SCC of 2 +/- 8 %. In a dose-response study, 50, 150, 500, and 1,500 mug/ml of fraction III from expanded rat kidney inhibited SCC by 4, 8, 19, and 28%, respectively; 500, 1,000 and 1,500 mug/ml inhibited Na-K-ATPase activity by 11, 22, and 49%, respectively. An identical study with fraction III from hydropenic animals showed no significant effect in either assay. Also, fractions from expanded and hydropenic rats, eluted after fraction III (fractions IV and V), had no effect on SCC or Na-K-ATPase activity. Fraction III also produced significant natriuresis in vivo at a dose of 500 mug/ml, confirming our observations that a natriuretic principle may be recovered from the kidneys of volume-expanded rats. We suggest that this natriuretic principle may act by reducing active sodium transport via inhibition of Na-K-ATPase.
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Urine volume and osmolality were studied in two schizophrenic patients with hyponatremia and six normal subjects after they smoked or ingested cigarettes. The results suggest that cigarette use may contribute to the development of hyponatremia by impairing water excretion.
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Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in a significant subset of schizophrenic patients. Case reports with methodological limitations suggest clozapine ameliorates this water imbalance. To more conclusively assess this possibility, we completed a 24-week open-label study in 8 male polydipsic hypoosmolemic schizophrenic inpatients. Subjects were treated initially for 6 weeks with a conventional neuroleptic, which was replaced by 300, 600, and 900 (if tolerated) mg/day of clozapine for sequential 6-week periods. On clozapine, mean plasma osmolality rose an average of 15.2 mosm/kg (95% CI: 5.5-25.0). Dosage of 300 mg/day of clozapine was sufficient to normalize plasma osmolality and was generally well tolerated. Clozapine appears to be the first effective pharmacotherapy for severe water imbalance in schizophrenia.
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