Involvement of dopamine receptor subtypes in dopaminergic modulation of aldosterone secretion in rats |
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Authors: | R J Barrett K F Wright D R Taylor A G Proakis |
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Institution: | 1. Department of Internal Medicine, Division of Vascular Medicine, Radboud University Medical Center, Nijmegen, Netherlands;2. Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands;3. Department of Radiology, Radboud University Medical Center, Nijmegen, Netherlands;4. Department of Urology, Radboud University Medical Center, Nijmegen, Netherlands;5. Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands;6. Department of Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands;7. Department of Hypertension, Institute of Cardiology, Warsaw, Poland;8. Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland;9. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, Netherlands;10. Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands;11. Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands;12. Department of Internal and Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands;13. Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany;1. Albert Einstein College of Medicine, Bronx, New York;2. Department of Surgery, Montefore Medical Center, Bronx, New York;3. Surgical Oncology, Department of Surgery, Montefiore Medical Center, Bronx, New York;4. Endocrinology, Department of Medicine, Montefiore Medical Center, Bronx, New York;5. Rutgers Cancer Institute, New Brunswick, New Jersey;6. Endocrine Surgery, Rutgers Cancer Institute, New Brunswick, New Jersey |
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Abstract: | The postulation that dopamine (DA) may tonically inhibit aldosterone (ALDO) secretion has arisen from the finding that metoclopramide, a non-selective DA receptor antagonist with prominent non-dopaminergic actions, stimulates ALDO secretion. Experiments were performed to determine: (a.) the ability of several non-specific and subtype-specific DA receptor antagonists to stimulate ALDO secretion, (b.) the subtype DA receptor involved in regulating ALDO secretion, and (c.) if ALDO responses were associated with changes in plasma Na+(pNa), K+(pK), or osmolality (pOsm). Blood samples were withdrawn from carotid arterial catheters in conscious, fasted male Sprague-Dawley rats before and following intra-arterial administration of lactated Ringer's placebo, furosemide (10 mg/kg), or one of several DA receptor antagonists. Furosemide stimulated ALDO, decreased pK, and left pNa and pOsm unchanged. The non-selective DA receptor antagonists metoclopramide (0.2, 0.6 mg/kg), rs-sulpiride (0.2 mg/kg), and haloperidol (0.1 mg/kg), and the DA-2 receptor antagonists domperidone (0.1 mg/kg) and s-sulpiride (0.1 mg/kg) each stimulated ALDO, and left pNa, pK, and pOsm unchanged. Conversely, the DA-1 receptor antagonists SCH 23390 (0.03, 0.1 mg/kg) and r-sulpiride (0.1 mg/kg) failed to stimulate ALDO, and left pNa, pK, and pOsm unaltered. These studies suggest that ALDO secretion in rats is modulated by a mechanism involving DA-2, but not DA-1 subtype receptors, and that the ALDO responses to DA receptor antagonism are independent of changes in pNa, pK, and pOsm. |
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