{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T18:14:19Z","timestamp":1751480059316,"version":"3.40.4"},"reference-count":41,"publisher":"S. Karger AG","issue":"5-6","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:p>&lt;i&gt;Background\/Aims:&lt;\/i&gt; 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. &lt;i&gt;Methods:&lt;\/i&gt; 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. &lt;i&gt;Results:&lt;\/i&gt; 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 \u00b5-receptor antagonist cyprodime, but not by naloxonazine, the \u00b5&lt;sub&gt;1&lt;\/sub&gt;-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&lt;sub&gt;ATP&lt;\/sub&gt;) channel blocker. Additionally, vasodilatation by loperamide was reduced by an inhibitor of protein kinase A (PKA) and enhanced by an inhibitor of phosphodiesterases. &lt;i&gt;Conclusion:&lt;\/i&gt; We suggest that loperamide can lower MAP in SHRs via \u00b5&lt;sub&gt;2&lt;\/sub&gt;-opioid receptor-dependent cAMP-PKA pathway that induces vascular relaxation by opening K&lt;sub&gt;ATP&lt;\/sub&gt; channels.<\/jats:p>","DOI":"10.1159\/000326084","type":"journal-article","created":{"date-parts":[[2011,4,13]],"date-time":"2011-04-13T13:32:14Z","timestamp":1302701534000},"page":"257-264","source":"Crossref","is-referenced-by-count":15,"title":["Activation of Peripheral Opioid \u00b5-Receptors in Blood Vessel May Lower Blood Pressure in Spontaneously Hypertensive 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