title: Impairment of intracerebral arteriole dilation responses after subarachnoid hemorrhage. Laboratory investigation.
abstract: OBJECTIVE
  Cerebrovascular dysfunction after subarachnoid hemorrhage (SAH) may contribute to ischemia, but little is known about the contribution of intracerebral arterioles. In this study, the authors tested the hypothesis that SAH inhibits the vascular reactivity of intracerebral arterioles and documented the time course of this dysfunction.
  
  
  METHODS
  Subarachnoid hemorrhage was induced using an endovascular filament model in halothane-anesthetized male Sprague-Dawley rats. Penetrating intracerebral arterioles were harvested 2, 4, 7, or 14 days postinsult, cannulated using a micropipette system that allowed luminal perfusion and control of luminal pressure, and evaluated for reactivity to vasodilator agents.
  
  
  RESULTS
  Spontaneous tone developed in all pressurized (60 mm Hg) intracerebral arterioles harvested in this study (from 66 rats), with similar results in the sham and SAH groups. Subarachnoid hemorrhage did not affect dilation responses to acidic pH (6.8) but led to a persistent impairment of endothelium-dependent dilation responses to adenosine triphosphate (p < 0.01), as well as a transient attenuation (p < 0.05) of vascular smooth muscle-dependent dilation responses to adenosine, sodium nitroprusside, and 8-Br-cyclic guanosine monophosphate (cGMP). Impairment of NO-mediated dilation was more sustained than adenosine- and 8-Br-cGMP-induced responses (up to 7 days postinsult compared with 2 days). All smooth muscle-dependent responses returned to sham levels by 14 days after SAH.
  
  
  CONCLUSIONS
  Subarachnoid hemorrhage led to a persistent impairment of endothelium-dependent dilation and a transient attenuation of vascular smooth muscle-dependent dilation responses to adenosine. Impairment of NO-mediated dilation occurred when the response to cGMP was intact, suggesting a change in cGMP levels rather than an alteration in intracellular mechanisms downstream from cGMP.
authors.affiliation: Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Ik-Seong
authors.initials: IS
authors.lastname: Park
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Meno
authors.forename: Cordelie E
authors.initials: CE
authors.lastname: Witt
authors.forename: Abhineet
authors.initials: A
authors.lastname: Chowdhary
authors.forename: Thien-Son
authors.initials: TS
authors.lastname: Nguyen
authors.forename: H Richard
authors.initials: HR
authors.lastname: Winn
authors.forename: Al C
authors.initials: AC
authors.lastname: Ngai
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Britz
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D002245:Carbon Dioxide; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D006152:Cyclic GMP; D000241:Adenosine; D010100:Oxygen