ANTAGONISTIC ACTIONS OF RENAL DOPAMINE AND 5-HYDROXYTRYPTAMINE - ENDOGENOUS 5-HYDROXYTRYPTAMINE, 5-HT1A RECEPTORS AND ANTINATRIURESIS DURING HIGH SODIUM-INTAKE

1 The present study has examined the effect of (+)-WAY 100135, a selec tive antagonist of 5-HT1A receptors, and ketanserin, an antagonist of 5-HT2 receptors, on the urinary excretion of Na+, K+, dopamine, 5-hydr oxytryptamine (5-HT) and their metabolites in rats treated with the se lective 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 (H S; 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 (DOP AC; 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 administrat ion 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+ increas ed 5.5 fold (from 6.7+/-0.2 to 36.5+/-0.9 mmol kg(-1) day(-1)), withou t 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 1 117.7+/-24.1 mOsm kg(-1) H2O). MAO-A inhibition during HS intake was f ound 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 16 0.4+/-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 cre atinine (from 29.1+/-2.3 to 28.4+/-2.1 mg kg(-1) day(-1)) excretion; u rine 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)), w as found to inhibit the antinatriuretic effect induced by Ro 41-1049 d uring HS intake. 5 It is suggested that MAO-A inhibition during HS int ake leads to an increased availability of 5-HT in renal tissues, the e ffect of which is a decrease in the urinary excretion of Na+, involvin g the activation of tubular 5-HT1A receptors.