Use of parenteral dipeptides to increase serum tyrosine levels and to enhance catecholamine-mediated neurotransmission

The use of intravascular tyrosine (TYR) to enhance Catecholamine release in hemorrhagic shock and other cardiovascular diseases, or as a constituent of nutrient mixtures used for total parenteral nutrition, is limited by the unusually poor solubility of the amino acid in water. We have thus examined the ability of various TYR-containing dipeptides, which are more water soluble than the amino acid, to raise serum TYR, to restore blood pressure in hemorrhaged hypotensive rats, and to lower blood pressure in spontaneously hypertensive rats (SHR). L-Tyrosyl-L-proline (TYR-PRO), L-tyrosyl-L-alanine (TYR-ALA), L-alanyl-L-tyrosine (ALA-TYR), and L-tyrosyl-L-tyrosine (TYR-TYR) given intravenously (12.5-25 mg/kg) all caused significant increases in serum TYR; the increase after TYR-PRO was dose related in the range 12.5-50 mg/kg. All of the dipeptides also caused significant elevations in blood pressure among hypotensive rats when administered intraarterially. Moreover, given intraperitoneally (100 mg/kg), all of them also lowered blood pressure in SHRs. These observations suggest that TYR-containing dipeptides may be useful in some clinical situations where maintaining or elevating blood TYR levels would be desirable.