title: Calcium sensitivity of vasospastic basilar artery after experimental subarachnoid hemorrhage.
abstract: Arteries that develop vasospasm after subarachnoid hemorrhage (SAH) may have altered contractility and compliance. Whether these changes are due to alterations in the smooth muscle cells or the arterial wall extracellular matrix is unknown. This study elucidated the location of such changes and determined the calcium sensitivity of vasospastic arteries. Dogs were placed under general anesthesia and underwent creation of SAH using the double-hemorrhage model. Vasospasm was assessed by angiography performed before and 4, 7, or 21 days after SAH. Basilar arteries were excised from SAH or control dogs (n = 8-52 arterial rings from 2-9 dogs per measurement) and studied under isometric tension in vitro before and after permeabilization of smooth muscle with alpha-toxin. Endothelium was removed from all arteries. Vasospastic arteries demonstrated significantly reduced contractility to KCl with a shift in the EC(50) toward reduced sensitivity to KCl 4 and 7 days after SAH (P < 0.05, ANOVA). There was reduced compliance that persisted after permeabilization (P < 0.05, ANOVA). Calcium sensitivity was decreased during vasospasm 4 and 7 days after SAH, as assessed in permeabilized arteries and in those contracted with BAY K 8644 in the presence of different concentrations of extracellular calcium (P < 0.05, ANOVA). Depolymerization of actin with cytochalasin D abolished contractions to KCl but failed to alter arterial compliance. In conclusion, it is shown for the first time that calcium sensitivity is decreased during vasospasm after SAH in dogs, suggesting that other mechanisms are involved in maintaining the contraction. Reduced compliance seems to be due to an alteration in the arterial wall extracellullar matrix rather than the smooth muscle cells themselves because it cannot be alleviated by depolymerization of smooth muscle actin.
authors.affiliation: Section of Neurosurgery (MC3026), University of Chicago Medical Center, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. rlmacdon@uchicago.edu
authors.forename: R Loch
authors.initials: RL
authors.lastname: Macdonald
authors.forename: Zhen-Du
authors.initials: ZD
authors.lastname: Zhang
authors.forename: Masataka
authors.initials: M
authors.lastname: Takahashi
authors.forename: Elena
authors.initials: E
authors.lastname: Nikitina
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.forename: An
authors.initials: A
authors.lastname: Xie
authors.forename: Lisa
authors.initials: L
authors.lastname: Larkin
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002533:Cerebral Angiography; D003187:Compliance / Q000187:drug effects; D003572:Cytochalasins / Q000494:pharmacology; D004285:Dogs; D007537:Isometric Contraction / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D010738:Type C Phospholipases / Q000494:pharmacology; D020301:Vasospasm, Intracranial / Q000503:physiopathology*
chemical_list: D002120:Calcium Channel Agonists; D003572:Cytochalasins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D010738:Type C Phospholipases; D002118:Calcium