{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:36:23Z","timestamp":1790415383120,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T00:00:00Z","timestamp":1562198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Endothelium\u2010dependent hyperpolarizations (EDHs) contribute to the regulation of peripheral resistance. They are initiated through opening of endothelial calcium\u2010activated potassium channels (K<jats:sub>Ca<\/jats:sub>); the potassium ions released then diffuse to the underlying smooth muscle cells, causing hyperpolarization and thus relaxation. The present study aimed to examine whether or not AMPK modulates EDH\u2010like relaxations in rat mesenteric arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Arterial rings were isolated for isometric tension recording. AMPK activity and protein level were measured by ELISA and western blotting respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The AMPK activator, AICAR, reduced ACh\u2010induced EDH\u2010like relaxations and increased AMPK activity in preparations with endothelium; these responses were prevented by compound C, an AMPK inhibitor. AICAR inhibited relaxations induced by SKA\u201031 (opener of endothelial K<jats:sub>Ca<\/jats:sub>) but did not affect potassium\u2010induced, hyperpolarization\u2010attributable relaxations or increase AMPK activity in preparations without endothelium. A769662, another AMPK activator, not only caused a similar inhibition of relaxations to ACh and SKA\u201031 in preparations with endothelium but also inhibited hyperpolarization\u2010attributable relaxations and augmented AMPK activity in rings without endothelium. Protein levels of total AMPK\u03b1, AMPK\u03b11, or AMPK\u03b21\/2 were comparable between preparations with and without endothelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Activation of endothelial AMPK, by either AICAR or A769662, acutely inhibits EDH\u2010like relaxations of rat mesenteric arteries. Furthermore, A769662 inhibits signalling downstream of smooth muscle hyperpolarization. In view of the major blunting effect of AMPK activation on EDH\u2010like relaxations, caution should be applied when administering therapeutic agents that activate AMPK in patients with endothelial dysfunction characterized by reduced production and\/or bioavailability of NO.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14716","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T18:04:58Z","timestamp":1558548298000},"page":"2905-2921","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Acute activation of endothelial AMPK surprisingly inhibits endothelium\u2010dependent hyperpolarization\u2010like relaxations in rat mesenteric arteries"],"prefix":"10.1111","volume":"176","author":[{"given":"Hui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR 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