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Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery
Abstract BACKGROUND Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive ra...
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| Published in: | American journal of hypertension 2020-07, Vol.33 (7), p.634-643 |
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| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c357t-b22a5f1a95759b1e5638b6d61f1e530abaf390120afd37e30ebd38f8e9c770de3 |
| container_end_page | 643 |
| container_issue | 7 |
| container_start_page | 634 |
| container_title | American journal of hypertension |
| container_volume | 33 |
| creator | Quek, Ko Jin Ameer, Omar Z Phillips, Jacqueline K |
| description | Abstract
BACKGROUND
Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive rat model of CKD, the Lewis Polycystic Kidney (LPK) rat.
METHODS
Mixed-sex LPK and Lewis control rats (total n = 38) were allocated to treated (amlodipine 20 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups. Following systolic blood pressure and renal function assessment, animals were euthanized and mesenteric vasculature was collected for functional and structural assessment using pressure myography and histology.
RESULTS
Amlodipine treatment reduced LPK rat blood pressure (untreated vs. treated: 185 ± 5 vs. 165 ± 9 mm Hg; P = 0.019), reduced plasma creatinine (untreated vs. treated: 197 ± 17 vs. 140 ± 16 µmol/l; P = 0.002), and improved some vascular structural parameters (internal and external diameters and wall–lumen ratios); however wall thickness was still increased in LPK relative to Lewis despite treatment (Lewis vs. LPK: 31 ± 2 vs. 41 ± 2 µm, P = 0.047). Treatment improved LPK rats’ endothelium dysfunction, and nitric oxide-dependent and endothelium-derived hyperpolarization vasorelaxation components, and downregulated prostanoid contributions. LTCC blockade had no effect on biomechanical properties of compliance and intrinsic stiffness, nor artery wall composition.
CONCLUSIONS
Our results indicate that blockade of LTCCs with amlodipine is effective in improving, to a certain extent, detrimental structural and functional vascular features of resistance arteries in CKD. |
| doi_str_mv | 10.1093/ajh/hpaa054 |
| format | article |
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BACKGROUND
Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive rat model of CKD, the Lewis Polycystic Kidney (LPK) rat.
METHODS
Mixed-sex LPK and Lewis control rats (total n = 38) were allocated to treated (amlodipine 20 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups. Following systolic blood pressure and renal function assessment, animals were euthanized and mesenteric vasculature was collected for functional and structural assessment using pressure myography and histology.
RESULTS
Amlodipine treatment reduced LPK rat blood pressure (untreated vs. treated: 185 ± 5 vs. 165 ± 9 mm Hg; P = 0.019), reduced plasma creatinine (untreated vs. treated: 197 ± 17 vs. 140 ± 16 µmol/l; P = 0.002), and improved some vascular structural parameters (internal and external diameters and wall–lumen ratios); however wall thickness was still increased in LPK relative to Lewis despite treatment (Lewis vs. LPK: 31 ± 2 vs. 41 ± 2 µm, P = 0.047). Treatment improved LPK rats’ endothelium dysfunction, and nitric oxide-dependent and endothelium-derived hyperpolarization vasorelaxation components, and downregulated prostanoid contributions. LTCC blockade had no effect on biomechanical properties of compliance and intrinsic stiffness, nor artery wall composition.
CONCLUSIONS
Our results indicate that blockade of LTCCs with amlodipine is effective in improving, to a certain extent, detrimental structural and functional vascular features of resistance arteries in CKD.</description><identifier>ISSN: 0895-7061</identifier><identifier>EISSN: 1941-7225</identifier><identifier>DOI: 10.1093/ajh/hpaa054</identifier><identifier>PMID: 32215654</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><ispartof>American journal of hypertension, 2020-07, Vol.33 (7), p.634-643</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2020</rights><rights>American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-b22a5f1a95759b1e5638b6d61f1e530abaf390120afd37e30ebd38f8e9c770de3</citedby><cites>FETCH-LOGICAL-c357t-b22a5f1a95759b1e5638b6d61f1e530abaf390120afd37e30ebd38f8e9c770de3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32215654$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quek, Ko Jin</creatorcontrib><creatorcontrib>Ameer, Omar Z</creatorcontrib><creatorcontrib>Phillips, Jacqueline K</creatorcontrib><title>Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery</title><title>American journal of hypertension</title><addtitle>Am J Hypertens</addtitle><description>Abstract
BACKGROUND
Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive rat model of CKD, the Lewis Polycystic Kidney (LPK) rat.
METHODS
Mixed-sex LPK and Lewis control rats (total n = 38) were allocated to treated (amlodipine 20 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups. Following systolic blood pressure and renal function assessment, animals were euthanized and mesenteric vasculature was collected for functional and structural assessment using pressure myography and histology.
RESULTS
Amlodipine treatment reduced LPK rat blood pressure (untreated vs. treated: 185 ± 5 vs. 165 ± 9 mm Hg; P = 0.019), reduced plasma creatinine (untreated vs. treated: 197 ± 17 vs. 140 ± 16 µmol/l; P = 0.002), and improved some vascular structural parameters (internal and external diameters and wall–lumen ratios); however wall thickness was still increased in LPK relative to Lewis despite treatment (Lewis vs. LPK: 31 ± 2 vs. 41 ± 2 µm, P = 0.047). Treatment improved LPK rats’ endothelium dysfunction, and nitric oxide-dependent and endothelium-derived hyperpolarization vasorelaxation components, and downregulated prostanoid contributions. LTCC blockade had no effect on biomechanical properties of compliance and intrinsic stiffness, nor artery wall composition.
CONCLUSIONS
Our results indicate that blockade of LTCCs with amlodipine is effective in improving, to a certain extent, detrimental structural and functional vascular features of resistance arteries in CKD.</description><issn>0895-7061</issn><issn>1941-7225</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kM9LwzAYhoMobk5P3iUnEaQuP5qmOY7hdDhRhnotafN1i7RpbVql_72VTY-e3pePhxe-B6FzSm4oUXyq37fTba01EeEBGlMV0kAyJg7RmMRKBJJEdIROvH8nhIRRRI_RiDNGRSTCMdrMyqIytrYO8LKsm-oTPH4D76HAi85lra0c1s7gNZSVgcK6DbYOt1vAK_iyHj9XRZ_1vrUZfrDGQY_XusWP4MG10AzXWTNkf4qOcl14ONvnBL0ubl_m98Hq6W45n62CjAvZBiljWuRUKyGFSimIiMdpZCKaD50TneqcK0IZ0bnhEjiB1PA4j0FlUhIDfIKudrvDKx8d-DYprc-gKLSDqvMJ43HIaKgkHdDrHZo1lfcN5End2FI3fUJJ8mM2Gcwme7MDfbEf7tISzB_7q3IALndA1dX_Ln0DnzyDQA</recordid><startdate>20200718</startdate><enddate>20200718</enddate><creator>Quek, Ko Jin</creator><creator>Ameer, Omar Z</creator><creator>Phillips, Jacqueline K</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20200718</creationdate><title>Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery</title><author>Quek, Ko Jin ; Ameer, Omar Z ; Phillips, Jacqueline K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-b22a5f1a95759b1e5638b6d61f1e530abaf390120afd37e30ebd38f8e9c770de3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quek, Ko Jin</creatorcontrib><creatorcontrib>Ameer, Omar Z</creatorcontrib><creatorcontrib>Phillips, Jacqueline K</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of hypertension</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quek, Ko Jin</au><au>Ameer, Omar Z</au><au>Phillips, Jacqueline K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery</atitle><jtitle>American journal of hypertension</jtitle><addtitle>Am J Hypertens</addtitle><date>2020-07-18</date><risdate>2020</risdate><volume>33</volume><issue>7</issue><spage>634</spage><epage>643</epage><pages>634-643</pages><issn>0895-7061</issn><eissn>1941-7225</eissn><abstract>Abstract
BACKGROUND
Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive rat model of CKD, the Lewis Polycystic Kidney (LPK) rat.
METHODS
Mixed-sex LPK and Lewis control rats (total n = 38) were allocated to treated (amlodipine 20 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups. Following systolic blood pressure and renal function assessment, animals were euthanized and mesenteric vasculature was collected for functional and structural assessment using pressure myography and histology.
RESULTS
Amlodipine treatment reduced LPK rat blood pressure (untreated vs. treated: 185 ± 5 vs. 165 ± 9 mm Hg; P = 0.019), reduced plasma creatinine (untreated vs. treated: 197 ± 17 vs. 140 ± 16 µmol/l; P = 0.002), and improved some vascular structural parameters (internal and external diameters and wall–lumen ratios); however wall thickness was still increased in LPK relative to Lewis despite treatment (Lewis vs. LPK: 31 ± 2 vs. 41 ± 2 µm, P = 0.047). Treatment improved LPK rats’ endothelium dysfunction, and nitric oxide-dependent and endothelium-derived hyperpolarization vasorelaxation components, and downregulated prostanoid contributions. LTCC blockade had no effect on biomechanical properties of compliance and intrinsic stiffness, nor artery wall composition.
CONCLUSIONS
Our results indicate that blockade of LTCCs with amlodipine is effective in improving, to a certain extent, detrimental structural and functional vascular features of resistance arteries in CKD.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>32215654</pmid><doi>10.1093/ajh/hpaa054</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| title | Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery |
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