| First Author | Gauthier KM | Year | 2011 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 300 |
| Issue | 3 | Pages | H725-35 |
| PubMed ID | 21193584 | Mgi Jnum | J:172618 |
| Mgi Id | MGI:5008366 | Doi | 10.1152/ajpheart.00696.2009 |
| Citation | Gauthier KM, et al. (2011) Role of arachidonic acid lipoxygenase metabolites in acetylcholine-induced relaxations of mouse arteries. Am J Physiol Heart Circ Physiol 300(3):H725-35 |
| abstractText | Arachidonic acid (AA) metabolites function as EDHFs in arteries of many species. They mediate cyclooxygenase (COX)- and nitric oxide (NO)-independent relaxations to acetylcholine (ACh). However, the role of AA metabolites as relaxing factors in mouse arteries remains incompletely defined. ACh caused concentration-dependent relaxations of the mouse thoracic and abdominal aorta and carotid, femoral, and mesentery arteries (maximal relaxation: 57 +/- 4%, 72 +/- 4%, 82 +/- 3%, 80 +/- 3%, and 85 +/- 3%, respectively). The NO synthase inhibitor nitro-L-arginine (L-NA; 30 muM) blocked relaxations in the thoracic aorta, and L-NA plus the COX inhibitor indomethacin (10 muM) inhibited relaxations in the abdominal aorta and carotid, femoral, and mesenteric arteries (maximal relaxation: 31 +/- 10%, 33 +/- 5%, 41 +/- 8%, and 73 +/- 3%, respectively). In mesenteric arteries, NO- and COX-independent relaxations to ACh were inhibited by the lipoxygenase (LO) inhibitors nordihydroguaiaretic acid (NDGA; 10 muM) and BW-755C (200 muM), the K(+) channel inhibitor apamin (1 muM), and 60 mM KCl and eliminated by endothelium removal. They were not altered by the cytochrome P-450 inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (20 muM) or the epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (10 muM). AA relaxations were attenuated by NDGA or apamin and eliminated by 60 mM KCl. Reverse-phase HPLC analysis revealed arterial [(14)C]AA metabolites that comigrated with prostaglandins, trihydroxyeicosatrienoic acids (THETAs), hydroxyepoxyeicosatrienoic acids (HEETAs), and hydroxyeicosatetraenoic acids (HETEs). Epoxyeicosatrienoic acids were not observed. Mass spectrometry confirmed the identity of 6-keto-PGF(1alpha), PGE(2), 12-HETE, 15-HETE, HEETAs, 11,12,15-THETA, and 11,14,15-THETA. AA metabolism was blocked by NDGA and endothelium removal. 11(R),12(S),15(S)-THETA relaxations (maximal relaxation: 73 +/- 3%) were endothelium independent and blocked by 60 mM KCl. Western immunoblot analysis and RT-PCR of the aorta and mesenteric arteries demonstrated protein and mRNA expression of leukocyte-type 12/15-LO. Thus, in mouse resistance arteries, 12/15-LO AA metabolites mediate endothelium-dependent relaxations to ACh and AA. |
