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Effect of dopamine antagonists on the urine flow of rats infused with hypotonic saline
Author(s) -
Angchanpen Pichian,
MarinGrez Marcos,
Schnermann Jürgen
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11416.x
Subject(s) - endocrinology , sulpiride , chemistry , medicine , diuresis , sch 23390 , antidiuretic , dopamine antagonist , dopamine , natriuresis , antagonist , haloperidol , tonicity , dopamine receptor , excretion , vasopressin , kidney , dopaminergic , receptor
1 The probable involvement of dopamine in the regulation of water excretion was investigated by administering dopamine antagonists intravenously to barbiturate ‐ anaesthetized rats undergoing a water diuresis induced by the infusion of 0.83% glucose with 0.3% NaCl at the rate of 9 ml h −1 . 2 Administration of 100 μg of the D 1 ‐/D 2 ‐dopamine antagonist, haloperidol, reduced the enhanced urine flow of rats infused with the hypotonic solution by 69% (from 75.4 ± 13.0 to 23.6 ± 6.0 μl min −1 , P < 0.01). Similarly, the D 1 ‐receptor antagonist, SCH 23390, reduced urine flow by 58% (from 77.5 ± 9.2 to 32.7 ± 7.2 μl min −1 , P < 0.01) and the D 2 ‐receptor antagonist, sulpiride, by 47% (from 66.2 ± 8.6 to 35.1 ± 6.8 μl min −1 , P < 0.05). 3 The injection of SCH 23390 increased the urine osmolality from 189.6 ± 27.5 to 479.8 ± 45.8 mosm kg −1 ( P < 0.05). There was no significant change in sodium and potassium excretion in any of the experiments. Blood pressure (BP) decreased after haloperidol and SCH 23390 injection from control values of 121.7 ±1.7 and 116.5 ±7.4 to 113.3 ±3.3 and 106.0 ± 8.8 mmHg respectively ( P < 0.05). 4 To study whether the influence of dopamine antagonists on urine flow during water diuresis depends on antidiuretic hormone (ADH), we administered 0.6 μg d(CH2)5‐D‐Phe‐Ile‐AVP (an ADH antagonist) shortly after the injection of 100 μg SCH 23390. The preferential V2 ADH‐antagonist abolished the antidiuretic effect of SCH 23390 but did not affect its blood pressure reducing effect (from 118.6 ± 5.6 to 103.2 ± 4.6 mmHg, P < 0.01). 5 These results suggest that dopamine antagonists blunted the hypotonic saline‐induced diuresis by favouring ADH release through an interference with an inhibitory dopaminergic pathway.