High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats

Abstract

Pinho MJ, Serrão MP, Soares-da-Silva P. High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats. Am J Physiol Renal Physiol 292: F1452-F1463, 2007. First published January 30, 2007 doi:10.1152/ajprenal.00465.2006.-This study evaluated in spontaneously hypertensive rats (SHR) and WistarKyoto rats (WKY) the response to salt loading of the renal dopaminergic system and transcript abundance of Na ϩ -independent (LAT1 and LAT2) and Na ϩ -dependent (ASCT2 and B 0 AT1) amino acid transporters potentially involved in renal tubular uptake of L-DOPA. Rats were fed normal (NS)-or high (HS; 1% saline as drinking water)-salt intake for 24 h. Transcript abundance of amino acid transporters was age dependent, differently regulated in WKY and SHR and responded differently to salt intake. HS intake similarly increased urinary dopamine in 4-wk-old SHR and WKY. At 12 wk of age, HS intake increased urinary dopamine in SHR, but not in WKY. Changes in urinary dopamine paralleled changes in the uptake of L-DOPA in isolated renal tubules from 4-and 12-wk-old WKY and SHR on NS and HS intake. At 12 wk of age, HS intake was accompanied by decreases in LAT1 and LAT2 transcript abundance in WKY and SHR. ASCT2 and B 0 AT1 expression was significantly decreased in both 4-and 12-wk-old WKY and in 4-wk-old SHR on HS intake. By contrast, HS intake increased ASCT2 and B 0 AT1 expression in 12-wk-old SHR. It is concluded that salt-sensitive mechanisms influence LAT1, LAT2, ASCT2, and B 0 AT1 gene transcription. Differences in urinary dopamine and tubular uptake of L-DOPA between WKY and SHR during HS intake, namely in 12-wk-old animals, may result from increases in the ASCT2 and B 0 AT1 mRNA levels and less pronounced decreases in LAT2 expression.LAT2; ASCT2; B 0 AT1; kidney; hypertension THE OCCURRENCE OF HYPERTENSION in humans and laboratory animals is associated with the disruption of normal sodium excretion (7). During moderate salt intake, renal dopamine as a result of D 1 -like receptor activation is responsible for ϳ50% of the sodium excretion (19,37,50). Sodium transport is modulated by renal dopamine, which has its origin in renal proximal tubule (RPT) cells and has been shown to act as an autocrine/paracrine substance (50). Dopamine-induced natriuresis that results from the activation of dopamine D 1 -like receptors is associated with decreases in the activities of the Na ϩ -K ϩ -ATPase and the Na ϩ -H ϩ exchanger (10,15,29,35,63). On the other hand, sodium has been found to constitute an important stimulus for the production of dopamine by RPT cells (53,54,56), resulting in increases in the urinary excretion of dopamine and dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) (3,14,18,60,61).The spontaneously hypertensive rat (SHR) is the most used experimental model for naturally occurring hypertension, in which salt loading amplifies the structural and functional cardiac and renal changes associated with long-standing hypertension (12). In the SHR, dopa...

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“…Circulating concentrations of dopamine are normally in the picomolar range, while dopamine levels in the kidney can reach high nanomolar concentrations [7]. The dopamine precursor L-DOPA (L-dihydroxy-phenylalanine) is taken up by the proximal tubule via multiple amino acid transporters, including rBat, LAT2 and ASCT2 [8, 9] from the circulation or following filtration at the glomerulus and is then converted to dopamine by aromatic amino acid decarboxylase (AADC), which is also localized to the proximal tubule [10]. There is evidence that intrarenal dopamine production is modulated by alterations in dietary salt intake [11, 12].…”

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“…Circulating concentrations of dopamine are normally in the picomolar range, while dopamine levels in the kidney can reach high nanomolar concentrations (4). The dopamine precursor l-dihydroxyphenylalanine (l-DOPA) is taken up by the proximal tubule via multiple amino acid transporters, including rBat, LAT2, and ASCT2 (5,6), from the circulation or after filtration at the glomerulus and is then converted to dopamine by aromatic amino acid decarboxylase (AADC), which is also localized to the proximal tubule (7). There is evidence that intrarenal dopamine production is modulated by alterations in dietary salt intake (8,9).…”