| Endothelial 15-lipoxygenase-1 overexpression increases acetylcholine-induced hypotension and vasorelaxation in rabbits. | |
| | |
MedLine Citation:
|
PMID: 18180398 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Nitin T Aggarwal; Yuttanna Chawengsub; Kathryn M Gauthier; Helena Viita; Seppo Yla-Herttuala; William B Campbell |
Related Documents
:
|
407938 - Effect of organic sulfur compounds on the chemical and enzymatic transformations of pro... 19218248 - Cyclooxygenase allosterism, fatty acid-mediated cross-talk between monomers of cyclooxy... 8371058 - Peroxisomal chain-shortening of thromboxane b2: evidence for impaired degradation of th... 21703598 - Mild acid hydrolysis of fucoidan: characterization by electrophoresis and ft-raman spec... 21360038 - Biphasic effect of linoleic acid on connexin 46 hemichannels. 3905208 - Measurement of blood cortisol and acid output in patients with duodenal ulceration and ... |
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 |
Affiliation:
|
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylcholine* Animals Arachidonate 15-Lipoxygenase / genetics, metabolism* Arachidonic Acid / metabolism Arteries / enzymology, physiopathology* Blotting, Western Endothelium, Vascular / enzymology* Gene Transfer Techniques Hemodynamics Humans Hypotension / chemically induced*, physiopathology Immunohistochemistry Isoenzymes / genetics, metabolism Isometric Contraction Liver / blood supply Mesenteric Arteries / physiopathology Rabbits Up-Regulation Vasodilation* Vasodilator Agents* |
| Grant Support | |
ID/Acronym/Agency:
|
HL-37981/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Isoenzymes; 0/Vasodilator Agents; 506-32-1/Arachidonic Acid; 51-84-3/Acetylcholine; EC 1.13.11.33/Arachidonate 15-Lipoxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Vitamin D deficiency and risk of cardiovascular disease.
Next Document: Hyperresistinemia is associated with coexistence of hypertension and type 2 diabetes.