Effect of High Salt Intake on the Expression of B0AT1 and LAT2 Amino Acid Transporters in Spontaneous Hypertensive Rat

Abstract

This study was performed to examine the response of two amino acid transport systems, potentially involved in L-DOPA uptake (Na+-independent LAT2 and Na+-dependent B0AT1) to salt load stimuli, in the renal cortex of the SHR and the normotensive Wistar-Kyoto rats (WKY). Animals were fed normal (NS) or high (HS - 1% saline as drinking water) salt diet for 24 hours. Kidney samples were collected, frozen in liquid N2, and stored at −80 degrees C before analysis for mRNA abundance. The renal dopaminergic system was evaluated: WKY failed to respond to HS with increases in the urinary dopamine excretion, at 12 weeks of age, while HS intake in SHR produced a 2-fold increase in the urinary excretion of dopamine. L-DOPA plasma levels in SHR during NS and HS intake were similar to those in WKY. RT-PCR quantification analysis revealed a decreased expression of LAT2 mRNA in WKY and SHR on HS intake. At 12 weeks of age, LAT2/4F2hc ratios in SHR on HS intake were significantly lower than in SHR fed a NS diet, which was not the case in WKY. Evaluation of the expression of Na+ dependent B0AT1, showed a significant decrease in both 4 and 12 week old WKY and in 4 week old SHR, fed HS diet. By contrast, HS intake produced a significant increase (~ 45% augment) in B0AT1 mRNA of SHR of 12 weeks of age. In conclusion, the increased renal dopamine production and excretion in SHR might be related to enhanced ability to take up L-DOPA at the kidney level. During HS, Na+ dependent B0AT1 is overexpressed in SHR kidney, probably contributing to the enhanced L-DOPA uptake, observed in the hypertensive phase. Differences in regulation of renal B0AT1 and LAT2 in SHR versus WKY may have to do with differences concerning sodium handling. Supported by grant POCTI/SAU-OBS/57916/2004.