Inhibitory effect of tuna peptide on endothelin production in cultured endothelial cells

The effect of tuna muscle-derived angiotensin-converting enzyme (ACE) inhibitory peptide (tuna AI) on the production of potent contracting factor, endothelin-1 (ET), in the cultured bovine aorta endothelial cells (BAECs) has been investigated. ET production in the culture medium was measured by radioimmunoassay. BAECs spontaneously produced ET in a time-dependent manner for 4 to 24 h after incubation. Addition of tuna AI to the medium resulted in a time- and concentration-dependent decrease in the production of ET. The tuna AI-induced inhibition of ET production was blocked by B-3824 (bradykinin (BK) B2-receptor antagonist), NG-monomethyl-L-Arg and indomethacin, but not by angiotensin II receptor antagonist. While BK, sodium nitroprusside and platelet-derived growth factor (PDGF) significantly inhibited ET production, angiotensin II and interleukin-1 did not. Potent ACE inhibitory peptides among tuna AI analogues did not always inhibit ET production. The results suggest that tuna AI inhibits ET production at least in part via potentiation of PDGF expression in addition to potentiation of BK pathway.