Cellular basis of vasospasm: role of small diameter arteries and voltage-dependent Ca2+ channels.
Constriction of small (100-200 microm) diameter cerebral arteries in response to increased intravascular pressure plays an important role in the regulation of cerebral blood flow. In arteries from healthy animals, these pressure-induced constrictions arise from depolarization of arterial smooth muscle leading to enhanced activity of L-type voltage-dependent calcium channels. Recently, we have observed that pressure-induced constrictions are greatly enhanced in cerebral arteries obtained from a rabbit model of subarachnoid hemorrhage (SAH) due to the emergence of R-type voltage-dependent calcium channels in arterial myocytes. Enhanced pressure-induced constrictions and the resulting decrease in cerebral blood may contribute to the development of neurological deficits in SAH patients following cerebral aneurysm rupture. This work supports the concept that small diameter arteries represent important targets for current treatment modalities (e.g. Hypertensive, Hypervolemic, Hemodilution "triple H" therapy) used in SAH patients. Further, we propose targeting R-type calcium channels, encoded by the gene Ca(v)2.3, as a novel therapeutic strategy in the treatment of SAH-induced cerebral vasospasm.
Ishiguro
M
M
Department of Pharmacology, Division of Neurological Surgery, University of Vermont College of Medicine, Burlington, VT 05405-0068, USA.
Wellman
G C
GC
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D011817:Rabbits; D012016:Reference Values; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology; D014652:Vascular Diseases / Q000503:physiopathology*; D020301:Vasospasm, Intracranial / Q000503:physiopathology
D015220:Calcium Channels; D020746:Calcium Channels, L-Type