Document Detail


Endothelial nitric oxide and 15-lipoxygenase-1 metabolites independently mediate relaxation of the rabbit aorta.
MedLine Citation:
PMID:  22197897     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelial 15-lipoxygenase-1 (15-LO-1) metabolites of arachidonic acid (AA), 11,12,15-trihydroxyeicosatrienoic acid (THETA) and 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) and nitric oxide (NO) mediate relaxations to acetylcholine (ACH). However, interactions between NO and the 15-LO-1 pathway have not been explored. Therefore, the effect of physiological and pharmacological concentrations of NO on 15-LO activity and relaxation was studied in rabbit aorta. In indomethacin-treated aortic rings, maximal ACH relaxations of 91.3±4.0%, decreased to 54.5±3.0% by the NO synthase inhibitor, nitro-l-arginine (LNA), to 49.8±3% by the guanylate cyclase (GC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, to 63.7±4.9% by the lipoxygenase (LO) inhibitor, nordihydroguaiaretic acid (NDGA) and were completely inhibited by the combination of LNA and NDGA. AA relaxations were not affected by GC inhibition but were reduced by LO inhibition. The NO donor, dipropylenetriamine-NONOate (DPTA) caused concentration-related relaxations (EC(50)=4.7×10(-6)M). Aortic metabolism of (14)C-AA to THETA and HEETA was not altered by EC(50) concentrations of DPTA but were reduced 10-fold by 10(-3)M DPTA. In LNA-treated aorta, DPTA (3×10(-6)M) caused relaxations of 38.2.5±4%. Maximum relaxations to ACH did not differ in the presence and absence 3×10(-6)M DPTA (49.5±5% and 44.2±4%, respectively). These results indicate that NO and 15-LO-1 act in parallel to mediate ACH relaxations and NO does not alter 15-LO-1 activity.
Authors:
Nitin T Aggarwal; Kathryn M Gauthier; William B Campbell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-16
Journal Detail:
Title:  Vascular pharmacology     Volume:  56     ISSN:  1879-3649     ISO Abbreviation:  Vascul. Pharmacol.     Publication Date:    2012 Jan-Feb
Date Detail:
Created Date:  2012-01-30     Completed Date:  2012-08-21     Revised Date:  2013-09-19    
Medline Journal Info:
Nlm Unique ID:  101130615     Medline TA:  Vascul Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  106-12     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / metabolism
Alkenes / pharmacology
Animals
Aorta / drug effects*,  metabolism
Arachidonate 15-Lipoxygenase / metabolism*
Arachidonic Acid / metabolism
Endothelium, Vascular / drug effects*,  metabolism
Guanylate Cyclase / antagonists & inhibitors
Indomethacin / pharmacology
Lipoxygenase Inhibitors / pharmacology
Muscle, Smooth, Vascular / drug effects*,  metabolism
Nitric Oxide / pharmacology*
Nitric Oxide Synthase / antagonists & inhibitors
Rabbits
Vasodilation / drug effects
Grant Support
ID/Acronym/Agency:
HL-103673/HL/NHLBI NIH HHS; HL-37981/HL/NHLBI NIH HHS; R01 HL037981/HL/NHLBI NIH HHS; R01 HL037981-22/HL/NHLBI NIH HHS; R01 HL103673/HL/NHLBI NIH HHS; R01 HL103673-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Alkenes; 0/Lipoxygenase Inhibitors; 0/dipropylenetriamine-NONOate; 10102-43-9/Nitric Oxide; 506-32-1/Arachidonic Acid; 51-84-3/Acetylcholine; 53-86-1/Indomethacin; EC 1.13.11.33/Arachidonate 15-Lipoxygenase; EC 1.14.13.39/Nitric Oxide Synthase; EC 4.6.1.2/Guanylate Cyclase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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