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α-乳吗啡肽可降低正常血压大鼠和自发性高血压大鼠通过无线电遥测法测得的血压。

Alpha-lactorphin lowers blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats.

作者信息

Nurminen M L, Sipola M, Kaarto H, Pihlanto-Leppälä A, Piilola K, Korpela R, Tossavainen O, Korhonen H, Vapaatalo H

机构信息

Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland.

出版信息

Life Sci. 2000;66(16):1535-43. doi: 10.1016/s0024-3205(00)00471-9.

Abstract

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.

摘要

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。

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