{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:52:31Z","timestamp":1780080751492,"version":"3.54.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["F31 HL142183"],"award-info":[{"award-number":["F31 HL142183"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["GRNT33680171"],"award-info":[{"award-number":["GRNT33680171"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Inhibition of adenosine kinase (ADK), via augmenting endogenous adenosine levels exerts cardiovascular protection. We tested the hypothesis that ADK inhibition improves microvascular dilator and left ventricle (LV) contractile function under metabolic or hemodynamic stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>In Obese diabetic Zucker fatty\/spontaneously hypertensive heart failure F1 hybrid rats, treatment with the selective ADK inhibitor, ABT\u2010702 (1.5\u00a0mg\/kg, intraperitoneal injections for 8\u2010week) restored acetylcholine\u2010, sodium nitroprusside\u2010, and adenosine\u2010induced dilations in isolated coronary arterioles, an effect that was accompanied by normalized end\u2010diastolic pressure (in mm\u00a0Hg, Lean: 3.4\u00a0\u00b1\u00a00.6, Obese: 17.6\u00a0\u00b1\u00a04.2, Obese\u00a0+\u00a0ABT: 6.6\u00a0\u00b1\u00a01.4) and LV relaxation constant, Tau (in ms, Lean: 6.9\u00a0\u00b1\u00a01.5, Obese: 13.9\u00a0\u00b1\u00a01.7, Obese\u00a0+\u00a0ABT: 6.0\u00a0\u00b1\u00a01.1). Mice with vascular endothelium selective ADK deletion (ADK<jats:sup>VEC<\/jats:sup>KO) exhibited an enhanced dilation to acetylcholine in isolated gracilis muscle (lgEC<jats:sub>50<\/jats:sub> WT: \u22128.2\u00a0\u00b1\u00a00.1, ADK<jats:sup>VEC<\/jats:sup>KO: \u22128.8\u00a0\u00b1\u00a00.1, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05) and mesenteric arterioles (lgEC<jats:sub>50<\/jats:sub> WT: \u22127.4\u00a0\u00b1\u00a00.2, ADK<jats:sup>VEC<\/jats:sup>KO: \u22128.1\u00a0\u00b1\u00a01.2, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05) when compared to wild\u2010type (WT) mice, whereas relaxation of the femoral artery and aorta (lgEC<jats:sub>50<\/jats:sub> WT: \u22127.03\u00a0\u00b1\u00a00.6, ADK<jats:sup>VEC<\/jats:sup>KO: \u22127.05\u00a0\u00b1\u00a00.8) was similar in the two groups. Wild\u2010type mice progressively developed LV systolic and diastolic dysfunction when they underwent transverse aortic constriction surgery, whereas ADK<jats:sup>VEC<\/jats:sup>\u2010KO mice displayed a lesser degree in decline of LV function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that ADK inhibition selectively enhances microvascular vasodilator function, whereby it improves LV perfusion and LV contractile function under metabolic and hemodynamic stress.<\/jats:p><\/jats:sec>","DOI":"10.1111\/micc.12624","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T19:08:26Z","timestamp":1588273706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Adenosine kinase inhibition enhances microvascular dilator function and improves left ventricle diastolic dysfunction"],"prefix":"10.1111","volume":"27","author":[{"given":"Alec","family":"Davila","sequence":"first","affiliation":[{"name":"Department of Physiology Medical College of Georgia Augusta University Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Georgia Augusta University Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Czikora","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical College of Georgia Augusta University Augusta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"S. 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