α-lactorphin and β-lactorphin improve arterial function in spontaneously hypertensive rats
- 作者：Sipola ; Marika ; Finckenberg ; Piet ; Vapaatalo ; Heikki ; Pihlanto-Leppä ; lä ; Anne ; Korhonen ; Hannu ; et. al.
- 关键词：α ; -lactorphin ; β ; -lactorphin ; Vascular function ; SHR ; NO
- 刊名：Life Sciences
- 出版年：2002
- 期刊代码：62_00243205
- 类别：imm
- 出版时间：August 2, 2002
- 卷：71
- 期：11
- 页码：1245-1253
- 文件大小：123 K
摘要
α-lactorphin (Tyr-Gly-Leu-Phe) lowers blood pressure in conscious adult SHR. This tetrapeptide is originally released from milk protein α-lactalbumin by enzymatic hydrolysis. In order to evaluate the antihypertensive mechanisms of α-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, β-lactorphin (Tyr-Leu-Leu-Phe), which originates from milk protein β-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 α-lactorphin or β-lactorphin. The role of nitric oxide (NO) is suggested, since this improvement was abolished by the NO synthase (NOS) inhibitor NG-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 α-lactorphin or β-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 β-lactorphin. The tetrapeptides did not alter vascular responses in mesenteric arteries from WKY. In conclusion, both α-lactorphin and β-lactorphin improved vascular relaxation in adult SHR in vitro. The beneficial effect of α-lactorphin was directed towards endothelial function, whereas β-lactorphin also enhanced endothelium-independent relaxation.