Published in:
Pharmacology, 87 (2011) 5-6, Seite 257-264
Language:
English
DOI:
10.1159/000326084
ISSN:
0031-7012;
1423-0313
Origination:
Footnote:
Description:
<i>Background/Aims:</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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 µ<sub>1</sub>-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 (K<sub>ATP</sub>) channel blocker. Additionally, vasodilatation by loperamide was reduced by an inhibitor of protein kinase A (PKA) and enhanced by an inhibitor of phosphodiesterases. <i>Conclusion:</i> We suggest that loperamide can lower MAP in SHRs via µ<sub>2</sub>-opioid receptor-dependent cAMP-PKA pathway that induces vascular relaxation by opening K<sub>ATP</sub> channels.