RELAXATION BY BRADYKININ IN PORCINE CILIARY ARTERY - ROLE OF NITRIC-OXIDE AND K-CHANNELS()

Purpose. To assess the effects K+-channel blockers on bradykinin-induc ed relaxations in porcine ciliary artery. Methods. Vascular isometric forces were measured with a myograph system. Ciliary vascular rings we re precontracted with thromboxane A(2) analog (U 46619, 10(-7) M) to a ssess dose-dependent (10(-10)-3 x 10(-6) M) bradykinin-induced relaxat ion after addition of one of the following: the nitric oxide (NO) synt hase inhibitor N omega-nitro-L-arginine methyl eater L-NAME, 10(-4) M) or inactive enantiomer (D-NAME, 10(-4) M); the nonspecific K+-channel blocker tetraethylammonium (TEA, 10(-2) M); or the ATP-sensitive K+-c hannel blocker glibenclamide (10(-5) M). The effect of TEA on relaxati ons to the NO donor, sodium nitroprusside (SNP, 10(-10)-10(-4) M) was investigated. The membrane potential of vascular smooth muscle cells ( VSMC) was recorded after exposure to bradykinin (2.5 X 10(-7) M). Resu lts. Endothelium-dependent relaxations to bradykinin (maximal [max], 9 9% +/- 3%) were strongly inhibited by L-NAME (max, 39% +/- 4%, P < 0.0 1) and partially by TEA (max, 62% +/- 3%, P < 0.01) or glibenclamide ( max, 77% +/- 4%, P < 0.01). Administration of glibenclamide plus L-NAM E further suppressed bradykinin-induced relaxation (max, 23% +/- 6%; P < 0.01), whereas TEA and L-NAME (max, 6% +/-2%; P < 0.01) abolished t he relaxation. SNP relaxations were unaffected by TEA. Bradykinin had no effect on the membrane potential of VSMC. Conclusions. In porcine c iliary artery, the endothelium-dependent relaxations to bradykinin are primarily mediated by NO and involve K+-channels. As only relaxations to bradykinin, but not those mediated by SNP, were inhibited by TEA, this implies that K+-channel blockers most likely affect the bradykini n-evoked NO production or release by the endothelium.