Activation of peripheral opioid μ-receptors in blood vessel may lower blood pressure in spontaneously hypertensive rats

Zhih Cherng Chen, Ja Ping Shieh, Hsien Hui Chung, Ching Hsia Hung, Hung Jung Lin, Juei Tang Cheng

研究成果: Article

13 引文 斯高帕斯(Scopus)

摘要

Background/Aims: The role of opioid receptors in the regulation of vascular function remains unclear. In the current study, we evaluated the ability of loperamide, a peripheral opioid receptor agonist, to regulate blood pressure in spontaneously hypertensive rats (SHRs) and examined the mechanism(s) by which loperamide exerts its effects. Methods: In male SHRs, mean arterial pressure (MAP) was measured and hemodynamic analysis was recorded. Additionally, the isometric tension of aortic rings isolated from SHRs was determined. Results: Loperamide dose-dependently decreased MAP in SHRs but not in the normal group of Wistar-Kyoto rats. This reduction of MAP in conscious SHRs was abolished by the selective opioid μ-receptor antagonist cyprodime, but not by naloxonazine, the μ1-opioid receptor antagonist. However, cardiac output was not altered by loperamide in anesthetized SHRs. Moreover, loperamide-induced relaxation in isolated aortic rings precontracted with phenylephrine or vasopressin. This relaxation was abolished by cyprodime, but not by naloxonazine. Loperamide-induced relaxation was also attenuated by glibenclamide, an ATP-sensitive potassium (KATP) channel blocker. Additionally, vasodilatation by loperamide was reduced by an inhibitor of protein kinase A (PKA) and enhanced by an inhibitor of phosphodiesterases. Conclusion: We suggest that loperamide can lower MAP in SHRs via μ2-opioid receptor-dependent cAMP-PKA pathway that induces vascular relaxation by opening KATP channels.

原文English
頁(從 - 到)257-264
頁數8
期刊Pharmacology
87
發行號5-6
DOIs
出版狀態Published - 2011 六月 1

All Science Journal Classification (ASJC) codes

  • Pharmacology

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