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Antagonistic actions of renal dopamine and 5‐hydroxytryptamine: endogenous 5‐hydroxytryptamine, 5‐HT 1A receptors and antinatriuresis during high sodium intake
Author(s) -
SoaresdaSilva P.,
VieiraCoelho M.A.,
Pestana M.
Publication year - 1996
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.1476-5381.1996.tb16715.x
Subject(s) - homovanillic acid , chemistry , endocrinology , dopamine , medicine , ketanserin , serotonin , receptor antagonist , monoamine oxidase , antagonist , receptor , 5 ht receptor , biochemistry , enzyme
1 The present study has examined the effect of (+)‐WAY 100135, a selective antagonist of 5‐HT 1A receptors, and ketanserin, an antagonist of 5‐HT 2 receptors, on the urinary excretion of Na + , K + , dopamine, 5‐hydroxytryptamine (5‐HT) and their metabolites in rats treated with the selective type A monoamine oxidase (MAO‐A) inhibitor, Ro 41–1049 (15 mg kg −1 day −1 ) in conditions of normal sodium (NS) and high sodium (HS; 1.0% NaCl in drinking water) intake. 2 Male Wistar rats were placed in metabolic cages and were given tap water (NS diet) in the first 4 days of the study and then challenged to a HS diet for another 7 days. Ro 41–1049 was given in drinking water only in the last 3 days of the HS diet, whereas (+)‐WAY 100135 (5 and 10 mg kg −1 day −1 , s.c.) or ketanserin (2 mg kg −1 day −1 , s.c.) were administered in the last 4 days of the HS intake period. 3 Daily urinary excretion (in nmol kg −1 day −1 ) of dopamine (82±2), 3,4‐dihydroxyphenylacetic acid (DOPAC; 198±9), homovanillic acid (HVA; 915±47), 5‐HT (586±37) and 5‐hydroxyindoleacetic acid (5‐HIAA; 1035±64) in the HS intake period was similar or higher than that in NS diet (dopamine = 68±2, DOPAC=197±4, HVA=923±42, 5‐HT = 539±132, 5‐HIAA = 1286±95). The administration of Ro 41–1049 on 3 consecutive days reduced the urinary excretion of dopamine, DOPAC and HVA, respectively, by 35–51% ( P <0.05), 73–85% ( P <0.05) and 59–66% ( P <0.05); the urinary excretion of 5‐HT increased 2 fold ( P <0.01) and the levels of 5‐HIAA were reduced by 39–77% ( P <0.05). 4 During HS intake (7 days), daily urinary excretion of Na + increased 5.5 fold (from 6.7±0.2 to 36.5±0.9 mmol kg −1 day −1 ), without changes in the urinary excretion of K + (from 11.2±0.2 to 11.9±0.5 mmol kg −1 day −1 ) and urinary osmolality (from 1083.8±26.7 to 1117.7±24.1 mOsm kg −1 H 2 O). MAO‐A inhibition during HS intake was found to produce a 47–68% decrease in Na + excretion (from 39.1±0.7 to 15.1±2.5 mmol kg −1 day −1 , n = 4; P <0.02) and urine volume (from 160.4±3.3 to 43.8±9.0 ml kg −1 day −1 , n = 4; P <0.02) without changes in K + (from 11.1±0.5 to 9.2±0.6 mmol kg −1 day −1 , n = 4) and creatinine (from 29.1±2.3 to 28.4±2.1 mg kg −1 day −1 ) excretion; urine osmolality increased 2 fold (from 936.3±40.3 to 2210.7±157.4 mOsm kg −1 H 2 O, n = 4; P <0.02). Administration of (+)‐WAY 100135 (5 and 10 mg kg −1 day −1 ), but not of ketanserin (2 mg kg −1 day −1 ), was found to inhibit the antinatriuretic effect induced by Ro 41–1049 during HS intake. 5 It is suggested that MAO‐A inhibition during HS intake leads to an increased availability of 5‐HT in renal tissues, the effect of which is a decrease in the urinary excretion of Na + , involving the activation of tubular 5‐HT iA receptors.