{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T23:29:02Z","timestamp":1772666942542,"version":"3.50.1"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Recent data from mesenteric and cerebral beds have revealed spatially restricted Ca\n              <jats:sup>2+<\/jats:sup>\n              transients occurring along the vascular intima that control effector recruitment and vasodilation. Although Ca\n              <jats:sup>2+<\/jats:sup>\n              is pivotal for coronary artery endothelial function, spatial and temporal regulation of functional Ca\n              <jats:sup>2+<\/jats:sup>\n              signals in the coronary endothelium is poorly understood.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              We aimed to determine whether a discrete spatial and temporal profile of Ca\n              <jats:sup>2+<\/jats:sup>\n              dynamics underlies endothelium-dependent relaxation of swine coronary arteries.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Using confocal imaging, custom automated image analysis, and myography, we show that the swine coronary artery endothelium generates discrete basal Ca\n              <jats:sup>2+<\/jats:sup>\n              dynamics, including isolated transients and whole-cell propagating waves. These events are suppressed by depletion of internal stores or inhibition of inositol 1,4,5-trisphosphate receptors but not by inhibition of ryanodine receptors or removal of extracellular Ca\n              <jats:sup>2+<\/jats:sup>\n              . In vessel rings, inhibition of specific Ca\n              <jats:sup>2+<\/jats:sup>\n              -dependent endothelial effectors, namely, small and intermediate conductance K\n              <jats:sup>+<\/jats:sup>\n              channels (K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 and K\n              <jats:sub>Ca<\/jats:sub>\n              2.3) and endothelial nitric oxide synthase, produces additive tone, which is blunted by internal store depletion or inositol 1,4,5-trisphosphate receptor blockade. Stimulation of endothelial inositol 1,4,5-trisphosphate\u2013dependent signaling with substance P causes idiosyncratic changes in dynamic Ca\n              <jats:sup>2+<\/jats:sup>\n              signal parameters (active sites, event frequency, amplitude, duration, and spatial spread). Overall, substance P\u2013induced vasorelaxation corresponded poorly with whole-field endothelial Ca\n              <jats:sup>2+<\/jats:sup>\n              measurements but corresponded precisely with the concentration-dependent change in Ca\n              <jats:sup>2+<\/jats:sup>\n              dynamics (linearly translated composite of dynamic parameters).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Our findings show that endothelium-dependent control of swine coronary artery tone is determined by spatial and temporal titration of inherent endothelial Ca\n              <jats:sup>2+<\/jats:sup>\n              dynamics that are not represented by tissue-level averaged Ca\n              <jats:sup>2+<\/jats:sup>\n              changes.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.115.308141","type":"journal-article","created":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T01:08:54Z","timestamp":1455498534000},"page":"1078-1090","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Functional Tuning of Intrinsic Endothelial Ca\n            <sup>2+<\/sup>\n            Dynamics in Swine Coronary Arteries"],"prefix":"10.1161","volume":"118","author":[{"given":"Michael","family":"Francis","sequence":"first","affiliation":[{"name":"From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua R.","family":"Waldrup","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Qian","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktoriya","family":"Solodushko","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Meriwether","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Taylor","sequence":"additional","affiliation":[{"name":"From the Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.18.4_suppl.ii90"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2003.10.001"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2009.12.023"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2010.07.016"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568006043481301"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.17.9747"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000217611.81085.c5"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.24.9265"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704551"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705057"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000081980.63146.69"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700928"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000238377.08219.0c"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.846634"},{"key":"e_1_3_5_17_2","first-page":"1075","article-title":"Nitric oxide and coronary vascular endothelium adaptations in hypertension.","volume":"5","author":"Levy AS","year":"2009","unstructured":"Levy AS, Chung JC, Kroetsch JT, Rush JW. 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