Circulatory activity of dopamine-dipeptide compounds

Three newly synthesized dopamine-dipeptide compounds (Gly-Pro-dopamide, Lys-Pro-dopamide, Z-Lys-Pro-dopamide) which should be cleft in vivo by the enzyme dipeptidyl peptidase IV (EC 3.4.14.5) were investigated as to their protective activity against hemorrhagic shock in rats. All three compounds increased significantly the survival times of animals, subjected to hemorrhage, in nearly the same manner as dopamine did. They also relaxed the blood vessels of isolated perfused rat kidneys pretreated with phenoxybenzamine. This activity demonstrates a vasodilation via dopaminergic receptors. Regarding the blood pressure increasing activity, mediated by excitation of alpha-receptors, Gly-Pro-dopamide was less potent than dopamine but affected blood pressure about four times longer than dopamine did. Lys-Pro-dopamide and Z-Lys-Pro-dopamide were nearly equieffective to dopamine.