Defining uremic arterial functional abnormalities in patients recently started on haemodialysis: combined in vivo and ex vivo assessment
Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vi...
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| Veröffentlicht in: | PloS one 2014-12, Vol.9 (12), p.e113462-e113462 |
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| creator | Abushufa, Adil M Eldehni, Mohamed T Odudu, Aghogho Evans, Philip D O'Sullivan, Saoirse E McIntyre, Chris W |
| description | Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD patients. Abdominal fat biopsies were obtained from 11 HD patients and 26 non-uremic controls. Subcutaneous arteries were dissected and mounted on a wire myograph, and cumulative concentration-response curves to noradrenalin, endothelin-1, a thromboxane A2 agonist (U46619), angiotensin II, vasopressin, bradykinin (BK), acetylcholine (ACh) and sodium nitroprusside (SNP) were constructed. Pulse wave velocity and blood pressure were measured in HD patients. Enhanced (P600 µm. The potency (pEC50) of U46619 (P |
| doi_str_mv | 10.1371/journal.pone.0113462 |
| format | Article |
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To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD patients. Abdominal fat biopsies were obtained from 11 HD patients and 26 non-uremic controls. Subcutaneous arteries were dissected and mounted on a wire myograph, and cumulative concentration-response curves to noradrenalin, endothelin-1, a thromboxane A2 agonist (U46619), angiotensin II, vasopressin, bradykinin (BK), acetylcholine (ACh) and sodium nitroprusside (SNP) were constructed. Pulse wave velocity and blood pressure were measured in HD patients. Enhanced (P<0.05-0.0001) maximal contractile responses (Rmax) to all spasmogens (particularly vasopressin) were observed in arteries from HD patients compared to controls, and this effect was more pronounced in arteries with an internal diameter>600 µm. The potency (pEC50) of U46619 (P<0.01) and vasopressin (P<0.001) was also increased in arteries>600 µm of HD patients. The maximal relaxant response to the endothelium-dependent dilators ACh and BK were lower in HD patients (P<0.01-P<0.0001) (worse for ACh than BK); however the endothelium-independent dilator SNP was similar in both groups. PWV was significantly correlated with the vasoconstrictor response to vasopressin (P = 0.042) in HD patients. HD patients are primed for hypertension and end organ demand ischaemia by a highly sensitised pressor response. The failure of arterial relaxation is mediated by endothelial dysfunction. Intrinsic vascular abnormalities may be important in sensitising HD patients to recurrent cumulative ischaemic end organ injury.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0113462</identifier><identifier>PMID: 25546407</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology ; Abnormalities ; Acetylcholine ; Acetylcholine - pharmacology ; Aged ; Angiotensin ; Angiotensin II ; Angiotensin II - pharmacology ; Angiotensins ; Arteries ; Arteries - physiopathology ; Biology and Life Sciences ; Blood pressure ; Bradykinin ; Bradykinin - pharmacology ; Calcification ; Chronic kidney failure ; Contractility ; Endothelin 1 ; Endothelin-1 - pharmacology ; Endothelins ; Endothelium ; Female ; Hemodialysis ; Hospitals ; Humans ; Hypertension ; Ischemia ; Kidney - physiopathology ; Kidney diseases ; Kidney transplantation ; Male ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Mortality ; Muscle Contraction - drug effects ; Muscle Relaxation - drug effects ; Myography ; Nitric oxide ; Nitroprusside - pharmacology ; Norepinephrine - pharmacology ; Patients ; Peritoneal dialysis ; Pituitary hormones ; Potassium ; Pulse Wave Analysis ; Renal Dialysis ; Rodents ; Sodium ; Sodium nitroprusside ; Thromboxane A2 ; Transplants & implants ; Uremia - physiopathology ; Vascular diseases ; Vasoconstrictor Agents - pharmacology ; Vasopressin ; Vasopressins - pharmacology ; Veins & arteries ; Wave velocity</subject><ispartof>PloS one, 2014-12, Vol.9 (12), p.e113462-e113462</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Abushufa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Abushufa et al 2014 Abushufa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-f33efbeb492a1cc1076aed6f76edd818d9bc2d64fd017963a608659791e4336d3</citedby><cites>FETCH-LOGICAL-c692t-f33efbeb492a1cc1076aed6f76edd818d9bc2d64fd017963a608659791e4336d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278673/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278673/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25546407$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abushufa, Adil M</creatorcontrib><creatorcontrib>Eldehni, Mohamed T</creatorcontrib><creatorcontrib>Odudu, Aghogho</creatorcontrib><creatorcontrib>Evans, Philip D</creatorcontrib><creatorcontrib>O'Sullivan, Saoirse E</creatorcontrib><creatorcontrib>McIntyre, Chris W</creatorcontrib><title>Defining uremic arterial functional abnormalities in patients recently started on haemodialysis: combined in vivo and ex vivo assessment</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD patients. Abdominal fat biopsies were obtained from 11 HD patients and 26 non-uremic controls. Subcutaneous arteries were dissected and mounted on a wire myograph, and cumulative concentration-response curves to noradrenalin, endothelin-1, a thromboxane A2 agonist (U46619), angiotensin II, vasopressin, bradykinin (BK), acetylcholine (ACh) and sodium nitroprusside (SNP) were constructed. Pulse wave velocity and blood pressure were measured in HD patients. Enhanced (P<0.05-0.0001) maximal contractile responses (Rmax) to all spasmogens (particularly vasopressin) were observed in arteries from HD patients compared to controls, and this effect was more pronounced in arteries with an internal diameter>600 µm. The potency (pEC50) of U46619 (P<0.01) and vasopressin (P<0.001) was also increased in arteries>600 µm of HD patients. The maximal relaxant response to the endothelium-dependent dilators ACh and BK were lower in HD patients (P<0.01-P<0.0001) (worse for ACh than BK); however the endothelium-independent dilator SNP was similar in both groups. PWV was significantly correlated with the vasoconstrictor response to vasopressin (P = 0.042) in HD patients. HD patients are primed for hypertension and end organ demand ischaemia by a highly sensitised pressor response. The failure of arterial relaxation is mediated by endothelial dysfunction. Intrinsic vascular abnormalities may be important in sensitising HD patients to recurrent cumulative ischaemic end organ injury.</description><subject>15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology</subject><subject>Abnormalities</subject><subject>Acetylcholine</subject><subject>Acetylcholine - pharmacology</subject><subject>Aged</subject><subject>Angiotensin</subject><subject>Angiotensin II</subject><subject>Angiotensin II - pharmacology</subject><subject>Angiotensins</subject><subject>Arteries</subject><subject>Arteries - physiopathology</subject><subject>Biology and Life Sciences</subject><subject>Blood pressure</subject><subject>Bradykinin</subject><subject>Bradykinin - pharmacology</subject><subject>Calcification</subject><subject>Chronic kidney failure</subject><subject>Contractility</subject><subject>Endothelin 1</subject><subject>Endothelin-1 - pharmacology</subject><subject>Endothelins</subject><subject>Endothelium</subject><subject>Female</subject><subject>Hemodialysis</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Ischemia</subject><subject>Kidney - physiopathology</subject><subject>Kidney diseases</subject><subject>Kidney transplantation</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle Relaxation - drug effects</subject><subject>Myography</subject><subject>Nitric oxide</subject><subject>Nitroprusside - pharmacology</subject><subject>Norepinephrine - pharmacology</subject><subject>Patients</subject><subject>Peritoneal dialysis</subject><subject>Pituitary hormones</subject><subject>Potassium</subject><subject>Pulse Wave Analysis</subject><subject>Renal Dialysis</subject><subject>Rodents</subject><subject>Sodium</subject><subject>Sodium nitroprusside</subject><subject>Thromboxane A2</subject><subject>Transplants & implants</subject><subject>Uremia - physiopathology</subject><subject>Vascular diseases</subject><subject>Vasoconstrictor Agents - pharmacology</subject><subject>Vasopressin</subject><subject>Vasopressins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>TestCollectionTL3OpenAccess</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abushufa, Adil M</au><au>Eldehni, Mohamed T</au><au>Odudu, Aghogho</au><au>Evans, Philip D</au><au>O'Sullivan, Saoirse E</au><au>McIntyre, Chris W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Defining uremic arterial functional abnormalities in patients recently started on haemodialysis: combined in vivo and ex vivo assessment</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-12-29</date><risdate>2014</risdate><volume>9</volume><issue>12</issue><spage>e113462</spage><epage>e113462</epage><pages>e113462-e113462</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD patients. Abdominal fat biopsies were obtained from 11 HD patients and 26 non-uremic controls. Subcutaneous arteries were dissected and mounted on a wire myograph, and cumulative concentration-response curves to noradrenalin, endothelin-1, a thromboxane A2 agonist (U46619), angiotensin II, vasopressin, bradykinin (BK), acetylcholine (ACh) and sodium nitroprusside (SNP) were constructed. Pulse wave velocity and blood pressure were measured in HD patients. Enhanced (P<0.05-0.0001) maximal contractile responses (Rmax) to all spasmogens (particularly vasopressin) were observed in arteries from HD patients compared to controls, and this effect was more pronounced in arteries with an internal diameter>600 µm. The potency (pEC50) of U46619 (P<0.01) and vasopressin (P<0.001) was also increased in arteries>600 µm of HD patients. The maximal relaxant response to the endothelium-dependent dilators ACh and BK were lower in HD patients (P<0.01-P<0.0001) (worse for ACh than BK); however the endothelium-independent dilator SNP was similar in both groups. PWV was significantly correlated with the vasoconstrictor response to vasopressin (P = 0.042) in HD patients. HD patients are primed for hypertension and end organ demand ischaemia by a highly sensitised pressor response. The failure of arterial relaxation is mediated by endothelial dysfunction. Intrinsic vascular abnormalities may be important in sensitising HD patients to recurrent cumulative ischaemic end organ injury.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25546407</pmid><doi>10.1371/journal.pone.0113462</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1640859627 |
| source | MEDLINE; TestCollectionTL3OpenAccess; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology Abnormalities Acetylcholine Acetylcholine - pharmacology Aged Angiotensin Angiotensin II Angiotensin II - pharmacology Angiotensins Arteries Arteries - physiopathology Biology and Life Sciences Blood pressure Bradykinin Bradykinin - pharmacology Calcification Chronic kidney failure Contractility Endothelin 1 Endothelin-1 - pharmacology Endothelins Endothelium Female Hemodialysis Hospitals Humans Hypertension Ischemia Kidney - physiopathology Kidney diseases Kidney transplantation Male Medicine Medicine and Health Sciences Middle Aged Mortality Muscle Contraction - drug effects Muscle Relaxation - drug effects Myography Nitric oxide Nitroprusside - pharmacology Norepinephrine - pharmacology Patients Peritoneal dialysis Pituitary hormones Potassium Pulse Wave Analysis Renal Dialysis Rodents Sodium Sodium nitroprusside Thromboxane A2 Transplants & implants Uremia - physiopathology Vascular diseases Vasoconstrictor Agents - pharmacology Vasopressin Vasopressins - pharmacology Veins & arteries Wave velocity |
| title | Defining uremic arterial functional abnormalities in patients recently started on haemodialysis: combined in vivo and ex vivo assessment |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T04%3A46%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Defining%20uremic%20arterial%20functional%20abnormalities%20in%20patients%20recently%20started%20on%20haemodialysis:%20combined%20in%20vivo%20and%20ex%20vivo%20assessment&rft.jtitle=PloS%20one&rft.au=Abushufa,%20Adil%20M&rft.date=2014-12-29&rft.volume=9&rft.issue=12&rft.spage=e113462&rft.epage=e113462&rft.pages=e113462-e113462&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0113462&rft_dat=%3Cgale_plos_%3EA417323179%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1640859627&rft_id=info:pmid/25546407&rft_galeid=A417323179&rft_doaj_id=oai_doaj_org_article_734ab9e15df1468f9f4dee518ac7c9e2&rfr_iscdi=true |