Central serotonergic alterations in deoxycorticosterone acetate/NaCl (DOCA/NaCl)-induced hypertension.
The present study investigated the metabolism of serotonin (5-HT) in rats made hypertensive by treatment with DOCA/NaCl. 5-Hydroxytryptamine and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were significantly elevated in a number of regions of the brain in rats treated for 2 weeks with DOCA/NaCl. Elevations in levels of 5-HIAA were present with 4 weeks of treatment with DOCA/NaCl but levels of 5-HT were not altered. No changes in the metabolism of 5-HT were detectable with 5 weeks of treatment with DOCA/NaCl. Levels of tryptophan were also elevated in a number of regions of the brain by treatment with DOCA/NaCl. Alterations in norepinephrine (NE) in the brainstem were present with 2, 4 or 5 weeks of treatment with DOCA/NaCl. The neurochemical effects of muscimol, a GABA agonist, were also investigated in rats treated with DOCA/NaCl for 4 weeks. Significant increases in levels of 5-HIAA and 5-HT were present in rats treated with DOCA/NaCl but not in controls, 15 min after intraventricular administration of muscimol (1.0 microgram/300 g body weight). Sixty min after muscimol, 5-HIAA was increased in both rats treated with DOCA/NaCl and control rats, but 5-HT was only increased in the hypothalamus. Treatment with DOCA/NaCl produced changes in the metabolism of 5-HT that may be important in the genesis of hypertension, but are not required for the maintenance of elevated arterial pressure. A disturbance of GABA-5-HT interactions between GABA and 5-HT in brainstem sites may also contribute to the pathogenesis of hypertension induced by DOCA/NaCl.
Department of Pharmacodynamics, College of Pharmacy, University of Florida, J. Hillis Miller Health Center, Gainesville 32610.
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Dawson
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Nagamhama
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Oparil
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000502:physiology; D003900:Desoxycorticosterone; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D012965:Sodium Chloride
D012701:Serotonin; D003900:Desoxycorticosterone; D012965:Sodium Chloride