| 18577383 |
Gupta PK, Subramani J, Leo MD, Sikarwar AS, Parida S, Prakash VR, Mishra SK: Role of voltage-dependent potassium channels and myo-endothelial gap junctions in 4-aminopyridine-induced inhibition of acetylcholine relaxation in rat carotid artery. Eur J Pharmacol. 2008 Sep 4;591(1-3):171-6. Epub 2008 Jun 12.
The present study examined the role of voltage-gated potassium (K (v)) channels and myo-endothelial gap junctions in 4-aminopyridine-induced inhibition of acetylcholine-evoked endothelium-dependent relaxation and NO release in the rat carotid artery. The acetylcholine-induced relaxation was drastically inhibited by 94% and 82%, respectively in the presence of either 100 microM N (G)-nitro-l-arginine methyl ester (L-NAME) or 10 microM 1H-[1,2,4] oxadiazolo [4,3,a] quinoxalin-1-one (ODQ), while it was abolished following endothelium removal. 4-aminopyridine (1 mM), a preferential blocker of the K (v) channels significantly decreased the vasodilator potency, as well as efficacy of acetylcholine (pD (2) 5.7+/-0.09, R (max) 86.1+/-3.5% versus control 6.7+/-0.10 R (max) 106+/-3.5%, n=6), but had no effect on the relaxations elicited by either sodium nitroprusside (SNP) or 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP). 4-AP (1 mM) also inhibited acetylcholine (3 microM)-stimulated nitrite release in the carotid artery segments (99.4+/-4.93 pmol/mg tissue weight wt; n=6 versus control 123.8+/-7.43 pmol/mg tissue weight wt, n=6). 18alpha-glycyrrhetinic acid (18alpha-GA, 5 microM), a gap junction blocker, completely prevented the inhibition of acetylcholine-induced relaxation, as well as nitrite release by 4-AP. In the pulmonary artery, however antagonism of acetylcholine-evoked relaxation by 4-AP was not reversed by 18alpha-GA. These results suggest that 4-AP-induced inhibition of endothelium-dependent relaxation and NO release involves electrical coupling between vascular smooth muscle and endothelial cells via myo-endothelial gap junctions in the rat carotid artery, but not in the pulmonary artery. Further, direct activation of 4-AP-sensitive vascular K (v) channels by endothelium-derived NO is not evident in the carotid blood vessel, while this appears to be an important mechanism of acetylcholine-induced relaxation in the pulmonary artery. |
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