Proposed mechanism of cerebral vasospasm: our hypothesis and current topics.
Increased vascular contractility plays an important role in the development of cerebral vasospasm following subarachnoid hemorrhage (SAH). Increased vascular contractility can be attributed to either endothelial dysfunction or increased contractility of vascular smooth muscle. Endothelial damage and dysfunction cause impairment of endothelium-dependent vasodilation of the cerebral artery after SAH. In addition to endothelial damage and dysfunction, receptor upregulation in vascular smooth muscle contributes to the induction and enhancement of contractile responses to agonists. Our recent data revealed that feedback regulation of the activity of the G protein-coupled receptor and myofilament Ca(2+) sensitivity is impaired after SAH. This impaired feedback regulation is suggested to cause a sustained contractile response to various agonists, thereby contributing to increased vascular contractility. In addition, three current topics are reviewed: endothelin type A receptor antagonists, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for treatment, and cortical spreading depolarization for the mechanism of cerebral vasospasm.
Department of Neurosurgery, Kyushu University, Fukuoka, Japan. tsasaki@ns.med.kyushu-u.ac.jp
Tomio
T
Sasaki
Yuichiro
Y
Kikkawa
D002118:Calcium / Q000378:metabolism; D013181:Cortical Spreading Depression / Q000502:physiology; D004146:Dioxanes / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009210:Myofibrils / Q000378:metabolism; D011725:Pyridines / Q000009:adverse effects; D011743:Pyrimidines / Q000009:adverse effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013449:Sulfonamides / Q000009:adverse effects; D013777:Tetrazoles / Q000009:adverse effects; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000209:etiology*
D004146:Dioxanes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; D013449:Sulfonamides; D013777:Tetrazoles; C109641:clazosentan; D002118:Calcium