{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:30:38Z","timestamp":1790523038726,"version":"4.1.0"},"reference-count":37,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:p>H<jats:sub>2<\/jats:sub>S is an endogenous gasotransmitter that increases cerebral blood flow. In the cerebral vascular endothelium, H<jats:sub>2<\/jats:sub>S is produced by cystathionine \u03b4-lyase (CSE). Endothelin-1 (ET-1) has constrictor and dilator influences on the cerebral circulation. The mechanism of the vasodilation caused by ET-1 may involve endothelium-derived factors. We hypothesize that ET-1-elicited dilation of pial arterioles requires an elevation of H<jats:sub>2<\/jats:sub>S production in the cerebral vascular endothelium. We investigated the effects of ET-1 on CSE-catalyzed brain H<jats:sub>2<\/jats:sub>S production and pial arteriolar diameter using cranial windows in newborn pigs in vivo. H<jats:sub>2<\/jats:sub>S was measured in periarachnoid cerebrospinal fluid. ET-1 (10<jats:sup>\u221212<\/jats:sup>\u201310<jats:sup>\u22128<\/jats:sup>M) caused an elevation of H<jats:sub>2<\/jats:sub>S that was reduced by the CSE inhibitors propargylglycine (PPG) and \u03b2-cyano-l-alanine (BCA). Low doses of ET-1 (10<jats:sup>\u221212<\/jats:sup>\u201310<jats:sup>\u221211<\/jats:sup>M) produced vasodilation of pial arterioles that was blocked PPG and BCA, suggesting the importance of H<jats:sub>2<\/jats:sub>S influences. The vasodilator effects of H<jats:sub>2<\/jats:sub>S may require activation of smooth muscle cell membrane ATP-sensitive K<jats:sup>+<\/jats:sup>(K<jats:sub>ATP<\/jats:sub>) channels and large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>(BK) channels. The K<jats:sub>ATP<\/jats:sub>inhibitor glibenclamide and the BK inhibitor paxilline blocked CSE\/H<jats:sub>2<\/jats:sub>S-dependent dilation of pial arterioles to ET-1. In contrast, the vasoconstrictor response of pial arterioles to 10<jats:sup>\u22128<\/jats:sup>M ET-1 was not modulated by PPG, BCA, glibenclamide, or paxilline and, therefore, was independent of CSE\/H<jats:sub>2<\/jats:sub>S influences. Pial arteriolar constriction response to higher levels of ET-1 was independent of CSE\/H<jats:sub>2<\/jats:sub>S and K<jats:sub>ATP<\/jats:sub>\/BK<jats:sub>Ca<\/jats:sub>channel activation. These data suggest that H<jats:sub>2<\/jats:sub>S is an endothelium-derived factor that mediates the vasodilator effects of ET-1 in the cerebral circulation via a mechanism that involves activation of K<jats:sub>ATP<\/jats:sub>and BK channels in vascular smooth muscle.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Disorders of the cerebral circulation in newborn infants may lead to lifelong neurological disabilities. We report that vasoactive peptide endothelin-1 exhibits vasodilator properties in the neonatal cerebral circulation by stimulating production of H<jats:sub>2<\/jats:sub>S, an endothelium-derived messenger with vasodilator properties. The ability of endothelin-1 to stimulate brain production of H<jats:sub>2<\/jats:sub>S may counteract the reduction in cerebral blood flow and prevent the cerebral vascular dysfunction caused by stroke, asphyxia, cerebral hypoxia, ischemia, and vasospasm.<\/jats:p>","DOI":"10.1152\/ajpheart.00451.2018","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T10:31:28Z","timestamp":1538130688000},"page":"H1759-H1764","source":"Crossref","is-referenced-by-count":26,"title":["H<sub>2<\/sub>S mediates the vasodilator effect of endothelin-1 in the cerebral circulation"],"prefix":"10.1152","volume":"315","author":[{"given":"Shalinkumar","family":"Patel","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander 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