Document Detail

Endothelial 15-lipoxygenase-1 overexpression increases acetylcholine-induced hypotension and vasorelaxation in rabbits.
MedLine Citation:
PMID:  18180398     Owner:  NLM     Status:  MEDLINE    
Arachidonic acid is metabolized by the 15-lipoxygenase-1 pathway to the vasodilatory eicosanoids hydroxy-epoxyeicosatrienoic acid and trihydroxyeicosatrienoic acid. We determined the in vitro and in vivo effects of the 15-lipoxygenase-1 metabolites in rabbits infected with adenovirus containing cDNA for human 15-lipoxygenase-1 (Ad-15-LO-1). Forty hours after intravenous adenoviral injection, 15-lipoxygenase-1 expression increased in liver and mesenteric arteries 10-fold and 3-fold, respectively. Expression of 15-LO-1 was limited to the endothelium of mesenteric arteries. Overexpression did not occur in tissues from rabbits infected with a beta-galactosidase containing adenovirus. Trihydroxyeicosatrienoic acid and hydroxy-epoxyeicosatrienoic acid synthesis per milligram of tissue increased by 2.1- and 1.5-fold, respectively, in mesenteric arteries from Ad-15-LO-1-infected rabbits compared with normal rabbits. Pretreatment with a 15-lipoxygenase inhibitor BW755C inhibited the synthesis. NO and prostaglandin-independent, maximal relaxations to acetylcholine were greater in mesenteric arteries from Ad-15-LO-1-infected rabbits (98.3+/-1.7%) compared with normal (60.93+/-10.5%) and beta-galactosidase containing adenovirus-infected rabbits (68.3+/-7.7%). Pretreatment with BW755C decreased these relaxations. Mean arterial pressure and heart rate did not differ in Ad-15-LO-1-infected rabbits compared with normal or beta-galactosidase containing adenovirus-infected rabbits. The hypotensive responses to acetylcholine in the presence and absence of inhibition of NO and prostaglandins were greater in Ad-15-LO-1-infected rabbits (-52+/-2% and -47+/-2%) compared with normal (-31+/-3% and -25+/-5%) or beta-galactosidase containing adenovirus-infected rabbits (-38+/-2% and -30+/-3%). Therefore, increased expression of 15-LO-1 increases acetylcholine relaxation in arteries and hypotensive responses in rabbits because of increased hydroxy-epoxyeicosatrienoic acid and trihydroxyeicosatrienoic acid synthesis.
Nitin T Aggarwal; Yuttanna Chawengsub; Kathryn M Gauthier; Helena Viita; Seppo Yla-Herttuala; William B Campbell
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-01-07
Journal Detail:
Title:  Hypertension     Volume:  51     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-24     Completed Date:  2008-02-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  246-51     Citation Subset:  IM    
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
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MeSH Terms
Arachidonate 15-Lipoxygenase / genetics,  metabolism*
Arachidonic Acid / metabolism
Arteries / enzymology,  physiopathology*
Blotting, Western
Endothelium, Vascular / enzymology*
Gene Transfer Techniques
Hypotension / chemically induced*,  physiopathology
Isoenzymes / genetics,  metabolism
Isometric Contraction
Liver / blood supply
Mesenteric Arteries / physiopathology
Vasodilator Agents*
Grant Support
Reg. No./Substance:
0/Isoenzymes; 0/Vasodilator Agents; 506-32-1/Arachidonic Acid; 51-84-3/Acetylcholine; EC 15-Lipoxygenase

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