title: Mechanism of ATP-induced local and conducted vasomotor responses in isolated rat cerebral penetrating arterioles.
abstract: BACKGROUND
  Adenosine triphosphate (ATP), a potent vascular regulator in the cerebral circulation, initiates conducted vasomotor responses which may be impaired after pathological insults. We analyzed the mechanism of ATP-induced local vasomotor responses and their effect on conducted vasomotor responses in rat cerebral penetrating arterioles.
  
  
  METHODS
  Arterioles were cannulated and their internal diameter monitored. Vasomotor responses to ATP were observed in the presence or absence of inhibitors, or after endothelial impairment. Smooth muscle membrane potentials were measured in some vessels.
  
  
  RESULTS
  Microapplication of ATP produced a biphasic response (constriction followed by dilation), which resulted in conducted dilation preceded by a membrane hyperpolarization. alpha,beta-methylene-ATP or pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) blunted the ATP-mediated constriction and enhanced local and conducted dilation. N(omega)-monomethyl-L-arginine, endothelial impairment and N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH) reduced the local dilation caused by ATP. The conducted dilation was attenuated by MS-PPOH and endothelial impairment, but not N(omega)-monomethyl-L-arginine or indomethacin.
  
  
  CONCLUSIONS
  ATP-induced conducted dilation is preceded by membrane hyperpolarization. Local ATP induces initial local constriction via smooth-muscle P(2X1) and subsequent dilation via endothelial P(2Y) receptors. Nitric oxide, cytochrome P450 metabolites, and intermediate and large conductance K(Ca) channels mediate dilation caused by ATP. ATP-induced conducted dilation is dependent upon both the endothelium and cytochrome P450 metabolites.
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. dietrichh@nsurg.wustl.edu
authors.forename: Hans H
authors.initials: HH
authors.lastname: Dietrich
authors.forename: Tetsuyoshi
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Chuanxi
authors.initials: C
authors.lastname: Xiang
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hongo
authors.forename: J Russell
authors.initials: JR
authors.lastname: Falck
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Dacey
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001685:Biological Factors / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000577:Amides; D001685:Biological Factors; C121756:N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide; D024681:Potassium Channels, Calcium-Activated; D011453:Prostaglandins; D018048:Receptors, Purinergic P2; C067410:endothelium-dependent hyperpolarization factor; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D009569:Nitric Oxide; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D003577:Cytochrome P-450 Enzyme System; C002630:alpha,beta-methyleneadenosine 5'-triphosphate