{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:33:25Z","timestamp":1788449605576,"version":"build-2803163510"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL-123647"],"award-info":[{"award-number":["R01 HL-123647"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15 HL-122922"],"award-info":[{"award-number":["R15 HL-122922"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008558","name":"Brody School of Medicine start-up funds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008558","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jsm.jsexmed.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The internal pudendal arteries (IPAs) supply blood to the penis and are highly susceptible to vascular remodeling in rodent models of diabetes, hypertension, aging, and chronic kidney disease, thus contributing to erectile dysfunction. Interestingly, vascular remodeling primarily occurs in the distal and not in the proximal IPA, suggesting distinct local physiologic signaling differences within the IPA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>To examine the role of purinergic signaling and neurotransmitter release by electrical field stimulation (EFS) in the regulation of proximal and distal IPA vascular tone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Proximal and distal IPAs were mounted in wire myographs and vascular responses to phenylephrine, acetylcholine, and 2-(N,N-diethylamino)-diazenolate-2-oxide, diethyl-ammonium salt (DEA NONOate) were measured. EFS-mediated contraction and non-adrenergic non-cholinergic (NANC) relaxation were evaluated in the absence and presence of a nitric oxide synthase antagonist. Purinergic agonist and NANC relaxation responses were assessed in the presence and absence of P2X1 and P2Y1 antagonists. Protein expression of P2X1 and P2Y1 receptors was measured by western blot.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Proximal and distal IPA contraction and relaxation were measured during increasing agonist administration and EFS in the presence and absence of antagonists.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Proximal and distal IPA concentration response curves to phenylephrine, acetylcholine, and DEA NONOate did no differ. Interestingly, distal IPA exhibited greater EFS-mediated contraction and NANC relaxation compared with proximal IPA. Nitric oxide synthase inhibition completely inhibited distal IPA NANC relaxation but did not affect proximal IPA relaxation. P2X1 or P2Y1 receptor antagonism during NANC\u00a0relaxation increased distal IPA relaxation but decreased proximal IPA relaxation. Combined P2X1 and P2Y1 receptor antagonism had no effect on proximal IPA relaxation but significantly increased distal IPA NANC relaxation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Translation<\/jats:title>\n                  <jats:p>Understanding neurovascular regulation of IPA vascular tone through nitrergic and purinergic mechanisms could yield new therapeutic targets to improve IPA blood flow and treat vasculogenic erectile dysfunction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Strengths and Limitations<\/jats:title>\n                  <jats:p>This study is the first to illustrate the differences in mechanisms responsible for regulating vascular tone in the proximal and distal IPAs. All presented findings are currently limited to ex\u00a0vivo vascular function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The regulation of vascular tone differs regionally in the IPA. The distal IPA is controlled through neurotransmitter-mediated NO-dependent mechanisms and increased sensitivity to purinergic P2X1 and P2Y1 receptor inhibition.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1016\/j.jsxm.2017.09.013","type":"journal-article","created":{"date-parts":[[2017,10,28]],"date-time":"2017-10-28T16:05:24Z","timestamp":1509206724000},"page":"1285-1296","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries"],"prefix":"10.1093","volume":"14","author":[{"given":"Michael R.","family":"Odom","sequence":"first","affiliation":[{"name":"Department of Physiology \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"Brody School of Medicine \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"East Carolina University \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena S.","family":"Pak","sequence":"additional","affiliation":[{"name":"Department of Physiology \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"Brody School of Medicine \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"East Carolina University \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Physiology \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"Brody School of Medicine \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"East Carolina University \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"Department of Human Nutrition, Foods, and Exercise \u00a0 , Blacksburg, VA ,","place":["USA"]},{"name":"Virginia Tech \u00a0 , Blacksburg, VA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna L.","family":"Hannan","sequence":"additional","affiliation":[{"name":"Department of Physiology \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"Brody School of Medicine \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]},{"name":"East Carolina University \u00a0 \u00a0 , Greenville, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"2024110504465833700_bib1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.amjmed.2006.06.010","article-title":"Prevalence and risk factors for erectile dysfunction in the US","volume":"120","author":"Selvin","year":"2007","journal-title":"Am J Med"},{"key":"2024110504465833700_bib2","first-page":"313","article-title":"The link between vasculogenic erectile dysfunction, coronary artery disease, and peripheral artery disease: role of 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