Human umbilical vein: involvement of cyclooxygenase-2 pathway in bradykinin B-1 receptor-sensitized responses

In isolated human umbilical vein (HUV), the contractile response to des-Arg (9)-bradykinin (des-Arg(9)-BK), selective BK B-1 receptor agonist, increase s as a function of the incubation time. Here, we evaluated whether cyclooxy genase (COX) pathway is involved in BK B-1-senzitized response obtained in 5-h incubated HUV rings. The effect of different concentrations of indometh acin, sodium salicylate, ibuprofen, meloxicam, lysine clonixinate or NS-398 administrated 30 min before concentration-response curves (CRC) was studie d. All treatments produced a significant rightward shift of the CRC to des- Arg(9)-BK in a concentration-dependent manner, which provides pharmacologic al evidence that COX pathway is involved in the BK B-1 responses. Moreover, in this tissue, the NS-398 pK(b) (5.2) observed suggests that COX-2 pathwa y is the most relevant. The strong correlation between published pIC(50) fo r COX-2 and the NSAIDs' pK(b)s estimated further supports the hypothesis th at COX-2 metabolites are involved in BK B-1 receptor-mediated responses. In other rings, indomethacin (30, 100 mu mol/l) or NS-398 (10, 30 mu mol/l) p roduced a significant rightward shift of the CRC to BK, selective BK B-2 ag onist, and its pKbs were similar to the values to inhibit BK B, receptor re sponses, suggesting that COX-2 pathway also is involved in BK B, receptor r esponses. Western blot analysis shows that COX-1 and COX-2 isoenzymes are p resent before and after 5-h in vitro incubation and apparently COX-2 does n ot suffer additional induction.