L-phenylalanine and smooth muscle cell proliferation from SHR and WKY rats

Cell growth and proliferation were evaluated in cultured vascular smooth muscle cells (VSMCs) isolated from spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat aortae by measuring [3H]-thymidine incorporation into newly synthesized DNA and by determining cell number, respectively. The results showed that in cultures from both rat strains (1) serum-, basic fibroblast growth factor (bFGF)- and thrombin-induced DNA synthesis were inhibited by L-phenylalanine dose-dependently; (2) L-phenylalanine inhibited cell proliferation in response to serum in a concentration-dependent manner; (3) L-phenylalanine inhibited serum-induced proto-oncogene c-fos and c-myc expression; (4) L-tyrosine, L-histidine and D-phenylalanine failed to mimic the inhibitory effect of L-phenylalanine. All these data demonstrate that L-phenylalanine could exert a direct and specific antiproliferative effect on VSMCs suggesting that such effect can account for the antihypertensive action of this amino acid observed in SHR.