{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:15:46Z","timestamp":1789600546830,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/20\/10260"],"award-info":[{"award-number":["PG\/20\/10260"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Raised serum concentrations of the sympathetic co\u2010transmitter neuropeptide Y (NPY) are linked to cardiovascular diseases. However, the signalling mechanism for vascular smooth muscle (VSM) constriction to NPY is poorly understood. Therefore, the present study investigated the mechanisms of NPY\u2010induced vasoconstriction in rat small mesenteric (RMA) and coronary (RCA) arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Third\u2010order mesenteric or intra\u2010septal arteries from male Wistar rats were assessed in wire myographs for isometric tension, VSM membrane potential and VSM intracellular Ca<jats:sup>2+<\/jats:sup> events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>NPY stimulated concentration\u2010dependent vasoconstriction in both RMA and RCA, which was augmented by blocking NO synthase or endothelial denudation in RMA. NPY\u2010mediated vasoconstriction was blocked by the selective Y<jats:sub>1<\/jats:sub> receptor antagonist BIBO 3304 and Y<jats:sub>1<\/jats:sub> receptor protein expression was detected in both the VSM and endothelial cells in RMA and RCA. The selective G\u03b2\u03b3 subunit inhibitor gallein and the PLC inhibitor U\u201073122 attenuated NPY\u2010induced vasoconstriction. Signalling via the G\u03b2\u03b3\u2013PLC pathway stimulated VSM Ca<jats:sup>2+<\/jats:sup> waves and whole\u2010field synchronised Ca<jats:sup>2+<\/jats:sup> flashes in RMA and increased the frequency of Ca<jats:sup>2+<\/jats:sup> flashes in myogenically active RCA. Furthermore, in RMA, the G\u03b2\u03b3 pathway linked NPY to VSM depolarization and generation of action potential\u2010like spikes associated with intense vasoconstriction. This depolarization activated L\u2010type voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> channels, as nifedipine abolished NPY\u2010mediated vasoconstriction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These data suggest that the G\u03b2\u03b3 subunit, which dissociates upon Y<jats:sub>1<\/jats:sub> receptor activation, initiates VSM membrane depolarization and Ca<jats:sup>2+<\/jats:sup> mobilisation to cause vasoconstriction. This model may help explain the development of microvascular vasospasm during raised sympathetic nerve activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16192","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T03:10:58Z","timestamp":1689649858000},"page":"3045-3058","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["G\u03b2\u03b3 subunit signalling underlies neuropeptide Y\u2010stimulated vasoconstriction in rat mesenteric and coronary arteries"],"prefix":"10.1111","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-204X","authenticated-orcid":false,"given":"JinHeng","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Scullion","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0848-6044","authenticated-orcid":false,"given":"Christopher J.","family":"Garland","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8014-2775","authenticated-orcid":false,"given":"Kim","family":"Dora","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","first-page":"52","article-title":"Effects of neuropeptide Y on contraction, relaxation, and membrane potential of rabbit cerebral arteries","volume":"13","author":"Abel P. 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