Antagonistic actions of renal dopamine and 5-hydroxytryptamine: Endogenous 5-hydroxytryptamine, 5-HT1A receptors and antinatriuresis during high sodium intake

Abstract

1. The present study has examined the effect of (+)-WAY 100135, a selective antagonist of 5-HT1A receptors, and ketanserin, an antagonist of 5-HT2 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 H2O). 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 H2O, 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-HT1A receptors.