{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:08:54Z","timestamp":1789880934289,"version":"4.0.1"},"reference-count":36,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:p>\n                    Systemic hypoxia causes skeletal muscle vasodilation, thereby preserving O\n                    <jats:sub>2<\/jats:sub>\n                    delivery to active tissues. Nitric oxide (NO), adenosine, and prostaglandins contribute to this vasodilation, but other factors may also play a role. We tested the hypothesis that regional inhibition of endothelium-derived hyperpolarizing factor with the cytochrome P-450 2C9 antagonist fluconazole, alone or combined with the NO synthase antagonist N\n                    <jats:sup>G<\/jats:sup>\n                    -monomethyl-l-arginine (l-NMMA), attenuates hypoxia-induced vasodilation. We compared forearm blood flow (FBF) and skin blood flow before and during brachial artery infusion of fluconazole (0.3 mg\/min; trial 1) or fluconazole + l-NMMA (50 mg over 10 min; trial 2) and during systemic hypoxia (10 min, arterial Po\n                    <jats:sub>2<\/jats:sub>\n                    \u223c37 mmHg) in infused (experimental) and control forearms of 12 healthy humans. During normoxia, fluconazole and fluconazole + l-NMMA reduced ( P &lt; 0.05) forearm vascular conductance (FVC) by \u223c10% and \u223c18%, respectively. During hypoxia and fluconazole ( trial 1), FVC increased by 1.76 \u00b1 0.37 and 0.95 \u00b1 0.35 units in control and experimental forearms, respectively ( P &lt; 0.05). During hypoxia and fluconazole + l-NMMA ( trial 2), FVC increased by 2.32 \u00b1 0.51 and 0.72 \u00b1 0.22 units in control and experimental forearms, respectively ( P &lt; 0.05). Similarly, during hypoxia with l-NMMA alone ( trial 3; n = 8) FVC increased by 1.51 \u00b1 0.46 and 0.45 \u00b1 0.32 units in control and experimental forearms, respectively ( P &lt; 0.05). These effects were not due to altered skin blood flow. We conclude that endothelium-derived hyperpolarizing factor contributes to basal vascular tone and to hypoxia-induced skeletal muscle vasodilation and could be particularly relevant when other vasodilator systems are impaired.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00073.2013","type":"journal-article","created":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T00:15:06Z","timestamp":1379376906000},"page":"H1639-H1645","source":"Crossref","is-referenced-by-count":16,"title":["Endothelium-derived hyperpolarizing factor contributes to hypoxia-induced skeletal muscle vasodilation in humans"],"prefix":"10.1152","volume":"305","author":[{"given":"Samson","family":"Spilk","sequence":"first","affiliation":[{"name":"Penn State Hershey Heart and Vascular Institute, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Herr","sequence":"additional","affiliation":[{"name":"Penn State Hershey Heart and Vascular Institute, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence I.","family":"Sinoway","sequence":"additional","affiliation":[{"name":"Penn State Hershey Heart and Vascular Institute, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs A.","family":"Leuenberger","sequence":"additional","affiliation":[{"name":"Penn State Hershey Heart and Vascular Institute, The Pennsylvania State University College of Medicine, The Milton S. 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