ROLE OF NON-NITRIC OXIDE NON-PROSTAGLANDIN ENDOTHELIUM-DERIVED RELAXING FACTOR(S) IN BRADYKININ VASODILATION

The most conspicuous effect of bradykinin following its administration into the systemic circulation is a transient hypotension due to vasod ilation. In the present study most of the available evidence regarding the mechanisms involved in bradykinin-induced arterial vasodilation i s reviewed, It has become firmly established that in most species vaso dilation in response to bradykinin is mediated by the release of endot helial relaxing factors following the activation of B-2-receptors, Alt hough in some cases the action of bradykinin is entirely mediated by t he endothelial release of nitric oxide (NO) and/or prostacyclin (PGI(2 )), a large amount of evidence has been accumulated during the last 10 years indicating that a non-NO/PGI(2) factor accounts for bradykinin- induced vasodilation in a wide variety of perfused vascular beds and i solated small arteries from several species including humans. Since th e effect of the non-NO/PGI(2) endothelium-derived relaxing factor is p ractically abolished by disrupting the K+ electrochemical gradient tog ether with the fact that bradykinin causes endothelium-dependent hyper polarization of vascular smooth muscle cells, the action of such facto r has been attributed to the opening of K+ channels in these cells, Th e pharmacological characteristics of these channels are not uniform am ong the different blood vessels in which they have been examined, Alth ough there is some evidence indicating a role for K-Ca or K-V channels , our findings in the mesenteric bed together with other reports indic ate that the K+ channels involved do not correspond exactly to any of those already described. In addition, the chemical identity of such hy perpolarizing factor is still a matter of controversy. The postulated main contenders are epoxyeicosatrienoic acids or endocannabinoid agoni sts for the CB1-receptors. Based on the available reports and on data from our laboratory in the rat mesenteric bed, we conclude that the NO /PGI(2)-independent endothelium-dependent vasodilation induced by BK i s unlikely to in involve a cytochrome P450 arachidonic acid metabolite or an endocannabinoid agonist.