Relaxation of porcine coronary artery to bradykinin. Role of arachidonic acid.
Bradykinin-induced relaxation of precontracted, porcine coronary artery (PCA) rings is mediated by distinctly different endothelium-derived relaxing factors depending on the contractile agent used. Thus when contracted with KCl, bradykinin-induced relaxation of PCA rings is mediated solely by nitric oxide (NO), whereas when contracted with the thromboxane mimetic U46619, a small component of the relaxation is attributable to NO and a large component is attributable to a non-NO mechanism that is independent of cyclooxygenase activity. We hypothesized that the non-NO component was mediated by arachidonic acid (AA) or by a non-cyclooxygenase product of AA metabolism. Bradykinin-induced relaxations of PCA rings precontracted with U46619 in the presence of indomethacin (10 mumol/L) were moderately attenuated by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 100 mumol/L), whereas when precontracted with KCl, L-NAME abolished the relaxations. AA produced endothelium-dependent relaxations of rings precontracted with U46619 that were unaffected by L-NAME, whereas AA did not relax rings precontracted with KCl. In rings precontracted with U46619, in the presence of L-NAME and indomethacin the phospholipase inhibitors quinacrine (50 mumol/L) and 4-bromophenacyl bromide (10 mumol/L) attenuated bradykinin- but not AA-induced relaxations. Inhibitors of both lipoxygenase (BW 755c [100 mumol/L] and nafazatrom [20 mumol/L]) and cytochrome P-450 (proadifen [10 mumol/L] and clotrimazole [10 mumol/L]) pathways did not eliminate bradykinin- or AA-induced relaxations, although clotrimazole partially attenuated AA-induced relaxations. These findings suggest that bradykinin-induced relaxation of PCA rings is mediated by AA through a mechanism that is not dependent on cyclooxygenase, lipoxygenase, or cytochrome P-450 pathways.
Weintraub
N L
NL
Department of Internal Medicine, Saint Louis University, School of Medicine, MO 63104.
Joshi
S N
SN
Branch
C A
CA
Stephenson
A H
AH
Sprague
R S
RS
Lonigro
A J
AJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D001158:Arteries / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D065607:Cytochrome P-450 Enzyme Inhibitors; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D010740:Phospholipases / Q000037:antagonists & inhibitors; D013552:Swine; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D065607:Cytochrome P-450 Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D010740:Phospholipases; D001920:Bradykinin