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

Abstract

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.

• Authors: Marika Sipola, Piet Finckenberg, Heikki Vapaatalo, Anne Pihlanto-Leppälä, Hannu Korhonen, Riitta Korpela, Marja-Leena Nurminen
• Journal: Life sciences (Life Sci) Vol. 71 Issue 11 Pg. 1245-53 (Aug 02 2002) ISSN: 0024-3205 [Print] Netherlands
• PMID: 12106590 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Acetylcholine (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Blood Pressure (drug effects)
• Enzyme Inhibitors (pharmacology)
• Hypertension (drug therapy, physiopathology)
• In Vitro Techniques
• Male
• Mesenteric Arteries (drug effects, 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)