Role of potassium channels in the nitric oxide-independent vasodilator response to acetylcholine.
Stimulation of vascular endothelial muscarinic receptors by acetylcholine (ACh) leads to the formation of an endothelium-derived relaxing factor (EDRF), which is generally accepted to be nitric oxide (NO). Recent evidence, however, suggests that NO may be only one of several EDRFs mediating the vasodilator response to ACh. Since this NO-independent vasodilator response to ACh has been hypothesized to be dependent upon K(+) channel activation, the current study was undertaken to investigate the role of K(+) channels in mediating the hindlimb vasodilator responses to ACh in vivo. Additionally, since variations in vascular tone can complicate the analysis of responses, the level of vascular tone was maintained at a similar level throughout the study so that responses could be compared directly. The results of the present study demonstrate that the vasodilator response to ACh possesses a significant component that is independent of NO production. The K(Ca) channel blockers charybdotoxin and apamin, but not K(+)-ATP channel blocker U37883A or the COX antagonist meclofenamate, attenuated the NO-independent component of the vasodilator response to ACh. This suggests that K(Ca) channels, but not K(+)-ATP channels or COX products, are involved in mediating the L-NAME resistant response to ACh. Further, the inhibition of the ACh vasodilator response by the K(+)-ATP opener BRL55834 suggests that the response is dependent upon membrane hyperpolarization. These data suggest that the mechanism mediating ACh responses in the hindlimb vascular bed of the rat are complex and may involve several signaling pathways.
Dabisch
Paul A
PA
Department of Pharmacology, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA70112, USA.
Liles
John T
JT
Taylor
James T
JT
Sears
Benjamin W
BW
Saenz
Rodrigo
R
Kadowitz
Philip J
PJ
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009569:Nitric Oxide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester