Abstract
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 KC1, 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. Bradykinininduced relaxations of PCA rings precontracted with U46619 in the presence of indomethacin (10 /imol/L) were moderately attenuated by the NO synthase inhibitor W-nitro-L-arginine methyl ester (L-NAME, 100 fxmolfL), whereas when precontracted with KC1, L-NAME abolished the relaxations. AA produced endothelium-dependent relaxations of rings precontraded with U46619 that were unaffected by L-NAME, whereas AA did not relax rings precontracted with KC1. In rings precontracted with U46619, in the presence of L-NAME and indomethacin the phospholipase inhibitors quinacrine (50 fimolfL) and 4-bromophenacyl bromide (10 jtmol/L) attenuated bradykinin- but not AA-induced relaxations. Inhibitors of both lipoxygenase (BW 755c [100 /imol/L] and nafazatrom [20 /xmol/L]) and cytochrome P-450 (proadifen [10 iimol/L] and clotrimazole [10 /xmol/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.
Original language | English (US) |
---|---|
Pages (from-to) | 976-981 |
Number of pages | 6 |
Journal | Hypertension |
Volume | 23 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1994 |
Externally published | Yes |
Keywords
- Arachidonic acid
- Bradykinin
- Coronary artery
- Endothelium-derived relaxing factor
ASJC Scopus subject areas
- Internal Medicine