Contribution of cytochrome P450 metabolites to bradykinin‐induced vasodilation in endothelial NO synthase deficient mouse hearts

Abstract
We have characterized the contribution of endothelial nitric oxide synthase (eNOS), cyclo‐oxygenase (COX) and cytochrome P450 (CYP450) to the bradykinin (BK)‐ induced vasodilation in isolated hearts from wildtype (WT) and eNOS deficient mice (eNOS−/−). The endothelium‐dependent vasodilation by bradykinin (BK, 1 μM) was significantly lower in eNOS−/− hearts than that in WT hearts (+247% and +325% of basal flow, respectively), while there was no difference in the endothelium‐independent vasodilation by adenosine. In WT hearts, the BK‐induced vasodilation was markedly attenuated following inhibition of NOS with ETU (10 μM) but not after COX inhibition with diclofenac (3 μM) (PBritish Journal of Pharmacology (2002) 135, 631–638; doi:10.1038/sj.bjp.0704472

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