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

• Type: Article in International Scientific Journal
• Date: 1996

Authors

soares-da-silva, p (Author) FMUP; vieira-coelho, ma (Author) Other; Pestana M (Author) FMUP

Journal

Title: British Journal of Pharmacology

Vol. 117

Pages: 1193-1198

ISSN: 0007-1188

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 14 Citations

Other information

Authenticus ID: P-001-EMV

Abstract (EN): 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 KS 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 mi 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6