{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:35:56Z","timestamp":1790516156466,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T00:00:00Z","timestamp":1444176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Local regulation of vascular resistance adjusts coronary blood flow to metabolic demand, although the mechanisms involved are not comprehensively understood<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that heart tissue surrounding rat coronary arteries releases diffusible factors that regulate vasoconstriction and relaxation<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Perivascular tissue reduces rho\u2010kinase\u2010dependent smooth muscle Ca<jats:sup>2+<\/jats:sup> sensitivity and constriction of coronary arteries to serotonin, the thromboxane analogue U46619 and the \u03b1<jats:sub>1<\/jats:sub>\u2010adrenergic agonist phenylephrine<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Endothelium\u2010dependent relaxation of coronary arteries in response to cholinergic stimulation is inhibited by perivascular tissue as a result of reduced endothelial Ca<jats:sup>2+<\/jats:sup>\u00a0responses and attenuated H<jats:sub>2<\/jats:sub>S\u2010dependent signalling<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results establish cellular mechanisms by which perivascular heart tissue can modify local vascular tone and coronary blood flow<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Interactions between perivascular tissue (PVT) and the vascular wall modify artery tone and contribute to local blood flow regulation. Using isometric myography, fluorescence microscopy, membrane potential recordings and phosphospecific immunoblotting, we investigated the cellular mechanisms by which PVT affects constriction and relaxation of rat coronary septal arteries. PVT inhibited vasoconstriction to thromboxane, serotonin and \u03b1<jats:sub>1<\/jats:sub>\u2010adrenergic stimulation but not to depolarization with elevated extracellular [K<jats:sup>+<\/jats:sup>]. When PVT was wrapped around isolated arteries or placed at the bottom of the myograph chamber, a smaller yet significant inhibition of vasoconstriction was observed. Resting membrane potential, depolarization to serotonin or thromboxane stimulation, and resting and serotonin\u2010stimulated vascular smooth muscle [Ca<jats:sup>2+<\/jats:sup>]\u2010levels were unaffected by PVT. Serotonin\u2010induced vasoconstriction was almost abolished by rho\u2010kinase inhibitor Y\u201027632 and modestly reduced by protein kinase C inhibitor bisindolylmaleimide X. PVT reduced phosphorylation of myosin phosphatase targeting subunit (MYPT) at Thr850 by \u223c40% in serotonin\u2010stimulated arteries but had no effect on MYPT\u2010phosphorylation in arteries depolarized with elevated extracellular [K<jats:sup>+<\/jats:sup>]. The net anti\u2010contractile effect of PVT was accentuated after endothelial denudation. PVT also impaired vasorelaxation and endothelial Ca<jats:sup>2+<\/jats:sup>\u00a0responses to cholinergic stimulation. Methacholine\u2010induced vasorelaxation was mediated by NO and H<jats:sub>2<\/jats:sub>S, and particularly the H<jats:sub>2<\/jats:sub>S\u2010dependent (<jats:sc>dl<\/jats:sc>\u2010propargylglycine\u2010 and XE991\u2010sensitive) component was attenuated by PVT. Vasorelaxation to NO\u2010 and H<jats:sub>2<\/jats:sub>S\u2010donors was maintained in arteries with PVT. In conclusion, cardiomyocyte\u2010rich PVT surrounding coronary arteries releases diffusible factors that reduce rho\u2010kinase\u2010dependent smooth muscle Ca<jats:sup>2+<\/jats:sup> sensitivity and endothelial Ca<jats:sup>2+<\/jats:sup>\u00a0responses. These mechanisms inhibit agonist\u2010induced vasoconstriction and endothelium\u2010dependent vasorelaxation and suggest new signalling pathways for metabolic regulation of blood flow.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp271006","type":"journal-article","created":{"date-parts":[[2015,9,9]],"date-time":"2015-09-09T11:47:03Z","timestamp":1441799223000},"page":"4747-4764","source":"Crossref","is-referenced-by-count":21,"title":["Perivascular tissue inhibits rho\u2010kinase\u2010dependent smooth muscle Ca<sup>2+<\/sup> sensitivity and endothelium\u2010dependent H<sub>2<\/sub>S signalling in rat coronary arteries"],"prefix":"10.1113","volume":"593","author":[{"given":"Filip","family":"Aalbaek","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth","family":"Bonde","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukhan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebbe","family":"Boedtkjer","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  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