Vasodilatory actions of the dietary peptide carnosine

The objective of this study was to test the hypothesis that the dietary dip eptide carnosine (beta-alanine-L-histidine) causes direct decreases in arte rial tone. Isolated descending thoracic aortic rings from male Sprague-Dawl ey rats were used for all studies. Preconstriction of vessels was accomplis hed with phenylephrine. Carnosine (0.625-20 mM) produced dose-dependent vas cular relaxation (P < 0.05) that was independent of endothelium. The consti tuent amino acid L-histidine did not produce any significant relaxation ove r the same dose range, whereas p-alanine actually produced dose-dependent v asoconstriction (P < 0.05). The soluble guanylate cyclase inhibitor methyle ne blue (10(-5) M) significantly decreased the relaxation produced by carno sine (P < 0.05). Measurement of cyclic GMP in the presence and absence of m ethylene blue after carnosine and phenylephrine exposure was also done. Met hylene blue 10-5 M resulted in a decrease in cyclic GMP levels from 65.3 +/ - 15.6 fmol/mg protein to 8.6 +/- 0.9 fmol/mg of protein (P = 0.001). We co nclude that carnosine produces relaxation of isolated rat aorta independent of endothelium. The effect of carnosine is at least in part mediated via c yclic GMP production and is not reproduced by its constituent amino acids, L-histidine and beta-alanine. (C) Elsevier Science Inc. 2000.