We studied the effects of various K+ channel blockers on the vasodilator responses of guinea-pig isolated basilar arteries to nitrergic nerve stimulation, the nitric oxide (NO) donor sodium nitroprusside (SNP), and the membrane permeable guanosine-3',5'-cyclic monophosphate (cyclic GMP) analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP). 2. In endothelium-denuded preparations which were contracted with prostaglandin F2alpha (1 microM), electrical field stimulation (EFS, 10 Hz for 30 s) produced a vasodilatation which was totally blocked by the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester L-NAME; 100 microM) (n=3) and by the selective NO-sensitive guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; 1 microM) (n=4). The vasodilator response to SNP (100 nM) was not reduced by L-NAME but was abolished by ODQ (1 microM) (n=4). 3. EFS-elicited vasodilatation was partly but significantly reduced by the non-selective K+ channel blockers tetraethylammonium (TEA, 1 and 3 mM) and 4-aminopyridine (4-AP, 3 mM), and by the large-conductance calcium-activated K+ channel (K(Ca) channel) blockers charybdotoxin (ChTX, 150 nM) and iberiotoxin (IbTX, 30 and 100 nM). In contrast, the ATP-sensitive K+ channel (K(ATP) channel) blocker glibenclamide (1-10 microM) and the small-conductance K(Ca) channel blocker apamin (100-500 nM) did not affect EFS-induced vasodilatation. 4. The vasodilator response elicited by SNP (10-100 nM) was significantly reduced by TEA (3 mM) and ChTX (150 nM) but not by apamin (500 nM) or glibenclamide (1 microM). The vasodilatation elicited by 8-Br-cyclic GMP (100 microM) was also reduced by TEA (3 mM) and ChTX (150 nM). 5. The results indicate that the vasodilatations induced by nitrergic nerve stimulation and the NO donor SNP in endothelium-denuded guinea-pig basilar artery depend on the formation of intracellular cyclic GMP. The increased cyclic GMP level activates large-conductance K(Ca) channels which partly mediate the vasodilator response. Neither K(ATP) channels nor apamin-sensitive small-conductance K(Ca) channels are involved in nitrergic transmitter-mediated vasodilatation.
