Nurminen M L, Sipola M, Kaarto H, Pihlanto-Leppälä A, Piilola K, Korpela R, Tossavainen O, Korhonen H, Vapaatalo H
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Life Sci. 2000;66(16):1535-43. doi: 10.1016/s0024-3205(00)00471-9.
Cardiovascular effects of subcutaneous administration of synthetic alpha-lactorphin, a tetrapeptide (Tyr-Gly-Leu-Phe) originally derived from milk alpha-lactalbumin, were studied in conscious spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY) with continuous radiotelemetric monitoring. Alpha-lactorphin dose-dependently lowered blood pressure (BP) without affecting heart rate in SHR and WKY. The lowest dose which reduced BP was 10 microg/kg, and the maximal reductions in systolic and diastolic BP (by 23+/-4 and 17+/-4 mm Hg, respectively) were observed at 100 microg/kg dose in SHR. No further reductions were obtained at a higher dose of 1 mg/kg. There were no significant differences in the BP responses to alpha-lactorphin between SHR and WKY. Naloxone (1 and 3 mg/kg s.c.), a specific opioid receptor antagonist, abolished the alpha-lactorphin-induced reduction in BP and reversed it into a pressor response, which provides evidence for an involvement of opioid receptors in the depressor action of the tetrapeptide.
采用连续无线电遥测监测技术,在清醒的自发性高血压大鼠(SHR)和正常血压的Wistar Kyoto大鼠(WKY)中研究了皮下注射合成α-乳白蛋白(一种最初从乳α-乳白蛋白衍生而来的四肽(Tyr-Gly-Leu-Phe))的心血管效应。α-乳白蛋白剂量依赖性地降低SHR和WKY的血压(BP),而不影响心率。降低血压的最低剂量为10μg/kg,在SHR中,100μg/kg剂量时观察到收缩压和舒张压的最大降幅(分别为23±4和17±4 mmHg)。在1 mg/kg的更高剂量下未获得进一步的降幅。SHR和WKY对α-乳白蛋白的血压反应无显著差异。特异性阿片受体拮抗剂纳洛酮(1和3 mg/kg皮下注射)消除了α-乳白蛋白引起的血压降低,并将其逆转成升压反应,这为阿片受体参与该四肽的降压作用提供了证据。