Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats

Life Sci. 2002 Aug 2;71(11):1245-53. doi: 10.1016/s0024-3205(02)01793-9.


alpha-lactorphin (Tyr-Gly-Leu-Phe) lowers blood pressure in conscious adult SHR. This tetrapeptide is originally released from milk protein alpha-lactalbumin by enzymatic hydrolysis. In order to evaluate the antihypertensive mechanisms of alpha-lactorphin, the effects of the tetrapeptide on vascular function were investigated in (30-35 weeks old) spontaneously hypertensive rats (SHR) with established hypertension and age-matched normotensive Wistar-Kyoto (WKY) rats in vitro. In addition, we studied the vascular effects of another structurally related tetrapeptide, beta-lactorphin (Tyr-Leu-Leu-Phe), which originates from milk protein beta-lactoglobulin. Endothelium-dependent relaxation to acetylcholine (ACh) was reduced in mesenteric arterial preparations of SHR as compared to those of WKY. In SHR, the ACh-induced relaxation was augmented by alpha-lactorphin or beta-lactorphin. The role of nitric oxide (NO) is suggested, since this improvement was abolished by the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Simultaneous potassium channel inhibitor tetraethylammonium (TEA) elicited no additional effect on the ACh-induced relaxation. The cyclooxygenase inhibitor diclofenac did not attenuate the augmented ACh relaxation induced by alpha-lactorphin or beta-lactorphin, suggesting that endothelial vasodilatory prostanoids were not involved in the effect of the tetrapeptides. Endothelium-independent relaxation to the NO donor sodium nitroprusside (SNP) was augmented in mesenteric arterial preparations of SHR by simultaneous beta-lactorphin. The tetrapeptides did not alter vascular responses in mesenteric arteries from WKY. In conclusion, both alpha-lactorphin and beta-lactorphin improved vascular relaxation in adult SHR in vitro. The beneficial effect of alpha-lactorphin was directed towards endothelial function, whereas beta-lactorphin also enhanced endothelium-independent relaxation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Hypertension / drug therapy
  • Hypertension / physiopathology*
  • In Vitro Techniques
  • Male
  • Mesenteric Arteries / drug effects*
  • Mesenteric Arteries / physiology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroprusside / pharmacology
  • Oligopeptides / pharmacology*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology


  • Antihypertensive Agents
  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Oligopeptides
  • Vasodilator Agents
  • alpha-lactorphin
  • beta-lactorphin
  • Nitroprusside
  • Nitric Oxide Synthase
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester