title: Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs.
abstract: OBJECTIVE
  Experiments were designed to determine the effect of subarachnoid hemorrhage on endothelium-dependent relaxations in small arteries of the brain stem. A "double-hemorrhage" canine model of the disease was used, and the presence of vasospasm in the basilar artery was confirmed by angiography.
  
  
  METHODS
  Secondary branches of both untreated basilar arteries (inner diameter, 324 +/- 11 microns; n = 12) and arteries exposed to subarachnoid hemorrhage for 7 days (inner diameter, 328 +/- 12 microns; n = 12) were dissected and mounted on glass microcannulas in organ chambers. Changes in the intraluminal diameter of pressurized arteries were measured using a video dimension analyzer.
  
  
  RESULTS
  In untreated arteries, 10(-11) to 10(-7) M vasopressin, 10(-10) to 10(-6) M bradykinin, and 10(-9) to 10(-6) M calcium ionophore A23187 caused endothelium-dependent relaxations. At 10(-6) and 3 x 10(-4) M the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) abolished relaxations to vasopressin and produced small but significant rightward shifts of the concentration-response curves to bradykinin and A23187. At 10(-3) M L-arginine prevented the inhibitory effect of L-NAME. Subarachnoid hemorrhage abolished relaxations to vasopressin but did not affect relaxations to bradykinin or A23187.
  
  
  CONCLUSIONS
  These studies suggest that in small arteries of the brain stem vasopressin causes relaxations by activation of the endothelial L-arginine pathway. This mechanism of relaxation is selectively inhibited by subarachnoid hemorrhage. Preservation of endothelium-dependent relaxations to bradykinin and A23187 is consistent with the concept that small arteries are resistant to vasospasm after subarachnoid hemorrhage.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minn. 55905.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Katusić
authors.forename: J H
authors.initials: JH
authors.lastname: Milde
authors.forename: F
authors.initials: F
authors.lastname: Cosentino
authors.forename: B S
authors.initials: BS
authors.lastname: Mitrović
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors; D001933:Brain Stem / Q000098:blood supply*; D000001:Calcimycin / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014664:Vasodilation; D014667:Vasopressins / Q000037:antagonists & inhibitors
chemical_list: D014667:Vasopressins; D000001:Calcimycin; D001120:Arginine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester