| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Phamacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
* To whom correspondence should be addressed. E-mail: wbcamp{at}mcw.edu.
We recently reported that the lipoxygenase product, 11,12,15-trihydroxyeicosatrienoic acid (THETA) mediates arachidonic acid (AA)-induced relaxation in rabbit aorta. This study was designed to determine whether this lipoxygenase metabolite is involved in relaxation responses to AA in rabbit small mesenteric arteries. AA (10-9-10-4M) produced potent relaxations in isolated phenylephrine-preconstricted arteries, with a maximal relaxation of 99±0.5% and EC50 of 50 nM. The cyclooxygenase (COX) inhibitors indomethacin (10 µM), NS-398 (10 µM; selective for COX-2), and SC-560 (100 nM; selective for COX-1) caused a marked rightward shift of concentration responses to AA. Using immunohistochemical analysis, both COX-1 and COX-2 were detected in endothelium and smooth muscle of small mesenteric arteries. The indomethacin-resistant relaxations were further reduced by lipoxygenase inhibitors cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC; 1 µM), nordihydroguaiaretic acid (NDGA, 1 µM), and ebselen (1 µM). High-performance liquid chromatography (HPLC) analysis showed that [14C] AA was metabolized by mesenteric arteries to PGI2, PGE2, THETAs, hydroxyepoxyeicosatrienoic acids (HEETAs), and 15-hydroxyeicosatetraenoic acid (15-HETE). The production of PGI2 and PGE2 was blocked by indomethacin, and the production of THETAs, HEETAs, and 15-HETE was inhibited by CDC and NDGA. Column fractions corresponding to THETAs were further purified and analyzed by gas chromatography/mass spectrometry, and were identified as 11,12,15- and 11,14,15-THETA. PGI2, PGE2, and purified THETA fractions relaxed mesenteric arteries precontracted with phenylephrine. The AA- and THETA-induced relaxations were blocked by high K+ (60 mM). These findings provide functional and biochemical evidence that AA-induced relaxation in rabbit small mesenteric arteries is mediated through both COX and lipoxygenase pathways.
This article has been cited by other articles:
|
|
 |
|
  Y. Chawengsub, K. M. Gauthier, K. Nithipatikom, B. D. Hammock, J. R. Falck, D. Narsimhaswamy, and W. B. Campbell Identification of 13-Hydroxy-14,15-epoxyeicosatrienoic Acid as an Acid-stable Endothelium-derived Hyperpolarizing Factor in Rabbit Arteries J. Biol. Chem., November 6, 2009; 284(45): 31280 - 31290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Foudi, X. Norel, M. Rienzo, L. Louedec, C. Brink, J.-B. Michel, and M. Back Altered reactivity to norepinephrine through COX-2 induction by vascular injury in hypercholesterolemic rabbits Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1882 - H1888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chawengsub, K. M. Gauthier, and W. B. Campbell Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H495 - H507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chawengsub, N. T. Aggarwal, K. Nithipatikom, K. M. Gauthier, S. Anjaiah, B. D. Hammock, J. R. Falck, and W. B. Campbell Identification of 15-hydroxy-11,12-epoxyeicosatrienoic acid as a vasoactive 15-lipoxygenase metabolite in rabbit aorta Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1348 - H1356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. T. Aggarwal, Y. Chawengsub, K. M. Gauthier, H. Viita, S. Yla-Herttuala, and W. B. Campbell Endothelial 15-Lipoxygenase-1 Overexpression Increases Acetylcholine-Induced Hypotension and Vasorelaxation in Rabbits Hypertension, February 1, 2008; 51(2): 246 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Stapleton, Adam. G. Goodwill, M. E. James, and J. C. Frisbee Altered mechanisms of endothelium-dependent dilation in skeletal muscle arterioles with genetic hypercholesterolemia Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1110 - R1119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. X. Zhang, K. M. Gauthier, Y. Chawengsub, and W. B. Campbell ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K+ Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H152 - H159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Bryan Jr., J. You, S. C. Phillips, J. J. Andresen, E. E. Lloyd, P. A. Rogers, S. E. Dryer, and S. P. Marrelli Evidence for two-pore domain potassium channels in rat cerebral arteries Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H770 - H780. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
