NO-mediated MaxiK(Ca) channel activation produces relaxation of guinea pigaorta independently of voltage-dependent L-type Ca2+ channels

The role of L-type Ca2+ channels in the relaxation to nitric oxide (NO)-med iated MaxiK(Ca) channel activation was examined in guinea pig aorta. Acetyl choline (ACh) produced an endothelium-dependent relaxation of guinea pig ao rta precontracted with noradrenaline (NA), which was abolished by an NO syn thase inhibitor, N-G-nitro-L-arginine (L-NNA). Both endothelium-dependent r elaxation by ACh and endothelium-independent relaxation by an NO donor, (+/ -)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR3), were strong ly suppressed by a soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,3]-ox adiazolo-[4,3-a]-quinoxalin-1-one (ODQ), suggesting that increased intracel lular cGMP plays the key role in both responses. ACh- and NOR3-induced rela xations were significantly suppressed by iberiotoxin (IbTX), a selective bl ocker of MaxiK(Ca) channels. ACh- and NOR3-induced relaxations were greatly attenuated when arteries were precontracted with high KCl instead of NA, s upporting the idea that K+ channel activation mediates the relaxant respons es. NOR3-induced relaxations were not affected by a L-type Ca2+ channel blo cker, diltiazem. Furthermore, endothelium-independent relaxation by a K-ATP channel opener, (+)-7,8-dihydro-6,6-dimethyl-7-hyroxy-8-(2-oxo-1-piperidin yl)-6H-pyrano[2,3-f]benz-2,1,3-oxadiazole (NIP-121) was nor affected by dil tiazem and nicardipine. These findings suggest that blockade of L-type Ca2 channels is not a major mechanism responsible for the vascular relaxation due to NO-mediated MaxiK(Ca) channel activation in guinea pig aorta. (C) 20 00 Elsevier Science Inc.