Endothelium-dependent regulation of cerebrovascular tone by extracellular and intracellular ATP.
ATP receptors and ATP-sensitive potassium channels (KATP) are expressed in vascular smooth muscle (VSM) and endothelial cells (EC). In isolated penetrating vessels, ATP caused a dilatation when applied intraluminally but not extraluminally. The actions of ATP were blocked by the nitric oxide (NO) synthesis inhibitor N omega-nitro-L-arginine (0.1 mM) but were only reduced by N-monomethyl-L-arginine (0.1 mM); responses to intraluminal ATP were also prevented by thapsigargin. The KATP opener (KCO) nicorandil (1 microM) caused an NO-independent vasodilatation when applied extraluminally and an NO-dependent response when applied intraluminally. Both responses were blocked by glibenclamide. EC-mediated responses to nicroandil were prevented by blockade of guanylate cyclase by LY-83583 (10 microM). The effects of nicorandil were mimicked by pinacidil (1-10 microM). Exposure of the endothelium to 500 microM cyanide and 0 mM glucose ("in vitro ischemia") caused a vasodilatation that was reduced by exposure to glibenclamide (5 microM). Blockade of NO synthase produced similar effects, suggesting that the ischemic dilation is mediated by KATP and NO. Our results suggest that both VSM and EC mediate the vascular responses induced by KCOs, whereas the dilatation induced by intraluminal ATP is mediated by the endothelium. The endothelium-dependent component of the in vitro ischemic vasodilatation is mediated by opening of endothelial KATP and subsequent release of NO.
Janigro
D
D
Department of Environmental Health, University of Washington Harborview Medical Center, Seattle 98104, USA.
Nguyen
T S
TS
Meno
J
J
West
G A
GA
Winn
H R
HR
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D008564:Membrane Potentials; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014666:Vasomotor System / Q000502:physiology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate