{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:51:03Z","timestamp":1791474663631,"version":"4.3.4"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81620108003"],"award-info":[{"award-number":["81620108003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018605","name":"Guangzhou Regenerative Medicine and Health Guangdong Laboratory","doi-asserted-by":"crossref","award":["2018GZR0201003"],"award-info":[{"award-number":["2018GZR0201003"]}],"id":[{"id":"10.13039\/501100018605","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018605","name":"Guangzhou Regenerative Medicine and Health Guangdong Laboratory","doi-asserted-by":"crossref","award":["2018GZR110102004"],"award-info":[{"award-number":["2018GZR110102004"]}],"id":[{"id":"10.13039\/501100018605","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Program of Introducing Talents of Discipline to Universities, 111 Plan","award":["D18005"],"award-info":[{"award-number":["D18005"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81521003"],"award-info":[{"award-number":["81521003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81922014"],"award-info":[{"award-number":["81922014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870473"],"award-info":[{"award-number":["81870473"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>\n                      Vascular smooth muscle cells (VSMCs) of resistance arteries receive sympathetic nerve signals, and subsequently elicit an endothelium-dependent anticontractile response to modulate vasoconstriction, but the specific role of this neurovascular transmission in hypertension in CKD is unknown. In this investigation,\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      models were used to study neurovascular transmission and its contribution to elevated vascular resistance in CKD, independent of vascular structural changes. The experiments revealed that the impaired anticontractile component of neurovascular transmission relies on sustained enhancement of sympathetic discharge, which is sensed at VSMCs and impairs expression of connexin 43 in gap junctions at myoendothelial junctions. This cascade interrupts endothelium-dependent hyperpolarizing responses and increases vascular tone. The findings provide new insights into the development of hypertension in CKD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertension commonly complicates CKD. Vascular smooth muscle cells (VSMCs) of resistance arteries receive signals from the sympathetic nervous system that induce an endothelial cell (EC)\u2013dependent anticontractile response that moderates vasoconstriction. However, the specific role of this pathway in the enhanced vasoconstriction in CKD is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A mouse model of CKD hypertension generated with 5\/6-nephrectomy (5\/6Nx) was used to investigate the hypothesis that an impaired anticontractile mechanism enhances sympathetic vasoconstriction.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      (isolated mesenteric resistance arteries), and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      (VSMC and EC coculture) models demonstrated neurovascular transmission and its contribution to vascular resistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>By 4 weeks, 5\/6Nx mice (versus sham) had augmented increases in mesenteric vascular resistance and mean arterial pressure with carotid artery occlusion, accompanied by decreased connexin 43 (Cx43) expression at myoendothelial junctions (MEJs), impaired gap junction function, decreased EC-dependent hyperpolarization (EDH), and enhanced contractions. Exposure of VSMCs to NE for 24 hours in a vascular cell coculture decreased MEJ Cx43 expression and MEJ gap junction function. These changes preceded vascular structural changes evident only at week 8. Inhibition of central sympathetic outflow or transfection of Cx43 normalized neurovascular transmission and vasoconstriction in 5\/6Nx mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>5\/6Nx mice have enhanced neurovascular transmission and vasoconstriction from an impaired EDH anticontractile component before vascular structural changes. These neurovascular changes depend on an enhanced sympathetic discharge that impairs the expression of Cx43 in gap junctions at MEJs, thereby interrupting EDH responses that normally moderate vascular tone. Dysregulation of neurovascular transmission may contribute to the development of hypertension in CKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020030234","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T21:02:27Z","timestamp":1593723747000},"page":"2312-2325","source":"Crossref","is-referenced-by-count":17,"title":["Sympathetic Overactivity in CKD Disrupts Buffering of Neurotransmission by Endothelium-Derived Hyperpolarizing Factor and Enhances Vasoconstriction"],"prefix":"10.1681","volume":"31","author":[{"given":"Wei","family":"Cao","sequence":"first","affiliation":[{"name":"Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, People\u2019s Republic of 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Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichen","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanjuan","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher 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