High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats.
This study evaluated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) the response to salt loading of the renal dopaminergic system and transcript abundance of Na(+)-independent (LAT1 and LAT2) and Na(+)-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.
Pinho
Maria João
MJ
Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal.
Serrão
Maria Paula
MP
Soares-da-Silva
Patrício
P
D000375:Aging / Q000378:metabolism; D026962:Amino Acid Transport System ASC / Q000235:genetics / Q000378:metabolism; D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D018377:Neurotransmitter Agents / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000494:pharmacology
D026962:Amino Acid Transport System ASC; D027182:Amino Acid Transport System y+; D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D027301:Fusion Regulatory Protein 1, Light Chains; D027283:Large Neutral Amino Acid-Transporter 1; D015778:Minor Histocompatibility Antigens; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; C520324:SLC6A19 protein, rat; C498849:Slc1a5 protein, rat; C486582:Slc7a8 protein, rat; D017673:Sodium Chloride, Dietary; D007980:Levodopa; D004298:Dopamine