{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:24:03Z","timestamp":1791721443414,"version":"4.3.4"},"reference-count":60,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"MINECO, Spain","award":["SAF 2012-31631"],"award-info":[{"award-number":["SAF 2012-31631"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n We assessed whether endothelin\u20101 (\n ET<\/jats:styled-content>\n \u20101) inhibits\n NO<\/jats:styled-content>\n and contributes to endothelial dysfunction in penile arteries in a model of insulin resistance\u2010associated erectile dysfunction (\n ED<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Vascular function was assessed in penile arteries, from obese (\n OZR<\/jats:styled-content>\n ) and lean (\n LZR<\/jats:styled-content>\n )\n Z<\/jats:styled-content>\n ucker rats, mounted in microvascular myographs. Changes in basal and stimulated levels of superoxide (\n \n O\n 2<\/jats:sub>\n \u2212<\/jats:sup>\n <\/jats:styled-content>\n ) were detected by lucigenin\u2010enhanced chemiluminescence and\n ET<\/jats:styled-content>\n receptor expression was determined by immunohistochemistry.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n ET<\/jats:styled-content>\n \u20101 stimulated acute\n \n O\n 2<\/jats:sub>\n \u2212<\/jats:sup>\n <\/jats:styled-content>\n production that was blunted by tempol and the\n NADPH<\/jats:styled-content>\n oxidase inhibitor, apocynin, but markedly enhanced in obese animals.\n ET<\/jats:styled-content>\n \u20101 inhibited the vasorelaxant effects of\n ACh<\/jats:styled-content>\n and of the\n NO<\/jats:styled-content>\n donor\n S<\/jats:styled-content>\n \u2010\n n<\/jats:styled-content>\n itroso\u2010\n N<\/jats:styled-content>\n \u2010acetyl\u2010\n DL<\/jats:styled-content>\n \u2010penicillamine in arteries from both\n LZR<\/jats:styled-content>\n and\n OZR<\/jats:styled-content>\n . Selective\n \n ET\n A<\/jats:sub>\n <\/jats:styled-content>\n (\n BQ123<\/jats:styled-content>\n ) or\n \n ET\n B<\/jats:sub>\n <\/jats:styled-content>\n receptor (\n BQ788<\/jats:styled-content>\n ) antagonists reduced both basal and\n ET<\/jats:styled-content>\n \u20101\u2010stimulated superoxide generation and reversed\n ET<\/jats:styled-content>\n \u20101\u2010induced inhibition of\n NO<\/jats:styled-content>\n \u2010mediated relaxations in\n OZR<\/jats:styled-content>\n , while only\n BQ\u2010<\/jats:styled-content>\n 123 antagonized\n ET<\/jats:styled-content>\n \u20101 actions in\n LZR<\/jats:styled-content>\n .\n ET<\/jats:styled-content>\n \u20101\u2010induced vasoconstriction was markedly enhanced by\n NO<\/jats:styled-content>\n synthase blockade and reduced by endothelium removal and apocynin. In endothelium\u2010denuded penile arteries, apocynin blunted augmented\n ET<\/jats:styled-content>\n \u20101\u2010induced contractions in\n OZR<\/jats:styled-content>\n . Both\n \n ET\n A<\/jats:sub>\n <\/jats:styled-content>\n and\n \n ET\n B<\/jats:sub>\n <\/jats:styled-content>\n receptors were expressed in smooth muscle and the endothelial layer and up\u2010regulated in arteries from\n OZR<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n ET<\/jats:styled-content>\n \u20101 stimulates\n \n ET\n A<\/jats:sub>\n <\/jats:styled-content>\n \u2010mediated\n NADPH<\/jats:styled-content>\n oxidase\u2010dependent\n ROS<\/jats:styled-content>\n generation, which inhibits endothelial\n NO<\/jats:styled-content>\n bioavailability and contributes to\n ET<\/jats:styled-content>\n \u20101\u2010induced contraction in healthy penile arteries. Enhanced vascular expression of\n \n ET\n B<\/jats:sub>\n <\/jats:styled-content>\n receptors contributes to augmented\n ROS<\/jats:styled-content>\n production, endothelial dysfunction and increased vasoconstriction in erectile tissue from insulin\u2010resistant obese rats. Hence, antagonism of\n \n ET\n B<\/jats:sub>\n <\/jats:styled-content>\n receptors might improve the\n ED<\/jats:styled-content>\n associated with insulin\u2010resistant states.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12870","type":"journal-article","created":{"date-parts":[[2014,8,4]],"date-time":"2014-08-04T08:28:20Z","timestamp":1407140900000},"page":"5682-5695","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Endothelin\u20101 contributes to endothelial dysfunction and enhanced vasoconstriction through augmented superoxide production in penile arteries from insulin\u2010resistant obese rats: role of\n \n ET\n A<\/sub>\n <\/scp>\n and\n \n ET\n B<\/sub>\n <\/scp>\n receptors"],"prefix":"10.1111","volume":"171","author":[{"given":"A","family":"S\u00e1nchez","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda Facultad de Farmacia Universidad Complutense de Madrid Madrid 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