ANGIOTENSIN-II STIMULATES SYSTEM Y(-ACID TRANSPORTER GENE-EXPRESSION IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS() AND CATIONIC AMINO)

The effect of angiotensin II (Ang II) on the transport of cationic ami no acids has been examined in vascular smooth muscle cells (VSMC) isol ated from rat aortae. Ang II stimulated the uptake rates of radiolabel ed arginine and lysine in a time- and concentration-dependent manner. The stimulated arginine uptake could be blocked by pretreatments with cycloheximide and actinomycin D or co-treatment with valsartan, an ant agonist specific for Ang II receptor subtype-1. The modulation by Ang II was bidirectional as the efflux of arginine was also stimulated, B- fold over basal. Using reverse transcription-coupled polymerase chain reaction methodology, a partial cDNA with 94% sequence identity to tha t of cationic amino acid transporter subtype-1 (CAT-1) of mouse fibrob lasts was obtained from VSMC. This sequence also exhibited 14 base cha nges compared with the sequence of ecotropic retrovirus receptor (ERR) /CAT-1 from rat hepatoma. Northern analyses with this partial CAT-1 cD NA and CAT-2 cDNA of mouse T-lymphocytes showed that Ang II rapidly st imulated the expression of both CAT-1 and CAT-2 in VSMC. Both signals peaked at 2 h after exposure to Ang II. The CAT-1 signal decayed over the next 6 h to levels 3-fold above basal, which are maintained up unt il 24 h. The induced CAT-2 mRNA concentration also decayed rapidly but increased again between 16 and 24 h to levels comparable with those o bserved at 2 h.