| 15464071 |
Guerard P, Goirand F, Fichet N, Bernard A, Rochette L, Morcillo EJ, Dumas M, Bardou M: Arachidonic acid relaxes human pulmonary arteries through K+ channels and nitric oxide pathways. Eur J Pharmacol. 2004 Oct 6;501(1-3):127-35.
We aimed to investigate the role of K (+) channels and nitric oxide (NO) on the relaxant effects of arachidonic acid in the human intralobar pulmonary arteries. Arachidonic acid produced a concentration-dependent relaxation (E (max)=93+/-3% of maximal relaxation induced by papaverine 0.1 mM;-log EC (30)=7.03+/-0.09) that was antagonized by the cyclooxygenase inhibitor indomethacin (1 microM), by the combination of cyclooxygenase blockade and cytochrome P450 (CYP) blockade with 17-octadecynoic acid (17-ODYA, 10 microM), by the combination of cyclooxygenase inhibition and NO synthase (NOS) inhibition with N (omega)-nitro-l-arginine (l-NOARG, 100 microM), by the simultaneous inhibition of CYP and NOS and by the simultaneous blockade of cyclooxygenase, CYP and NOS. Arachidonic acid-induced relaxation was significantly inhibited by glibenclamide (1 microM, ATP-dependent K (+) channel (K (ATP)) blocker), apamin and charybdotoxin (0.3 microM small (SK (Ca)) and 0.1 microM big (BK (Ca)) conductance Ca (2+)-sensitive K (+) channel blocker, respectively), and 4-aminopyridine (1 mM, voltage-dependent K (+) channel (K (V)) blocker). Indomethacin and ketoconazole suppressed the antagonistic effects of glibenclamide and apamin and 17-ODYA those of all the K (+) channel blockers tested. l-NOARG suppressed only the antagonistic effect of glibenclamide. We suggest that K (ATP), SK (Ca), BK (Ca) and K (V) are involved in the arachidonic acid-induced relaxation of human pulmonary arteries. Cyclooxygenase metabolites are the main relaxing agents of arachidonic acid, involving K (ATP) and SK (Ca) channels. CYP-dependent metabolites modulate arachidonic acid-induced relaxation through a pathway involving K (+) channels. K (ATP) channels are involved through a NOS-dependent pathway. |
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