• Gail J Pyne-Geithman, Danielle N Caudell, Matthew Cooper, Joseph F Clark, and Lori A Shutter.
• Department of Neurology, University of Cincinnati, 3125 Eden Avenue, 2324 Vontz Center, Cincinnati, OH 45267-0536, USA. pynegj@ucmail.uc.edu
• Neurocrit Care. 2009 Jan 1; 10 (2): 225231225-31.

IntroductionCerebral vasospasm after subarachnoid hemorrhage (SAH) is a serious complication resulting in delayed neurological deficit, increased morbidity, mortality, longer hospital stays, and rehabilitation time. It afflicts approximately 35 per 100,000 Americans per year, and there is currently no effective therapy. We present in vitro data suggesting that increasing intrinsic nitric oxide relaxation pathways in vascular smooth muscle via dopaminergic agonism ameliorates cerebral vasospasm after SAH.MethodsCerebrospinal fluid (CSF) from patients with cerebral vasospasm after SAH (CSF(V)) was used to induce vasospasm in porcine carotid artery in vitro. Dopamine was added to test its ability to reverse spasm, and specific dopamine receptor antagonists were used to determine which receptor mediated the protection. Immunohistochemical techniques confirmed the presence of dopamine receptor subtypes and the involvement of NOS in the mechanism of dopamine protection.ResultsDopamine receptor 1, 2, and 3 subtypes are all present in porcine carotid artery. Dopamine significantly reversed spasm in vitro (67% relaxation), and this relaxation was prevented by Haloperidol, a D(2)R antagonist (10% relaxation, P < 0.05), but not by D(1) or D(3)-receptor antagonism. Both eNOS and iNOS expression were increased significantly in response to CSF(V) alone, and this was significantly enhanced by addition of dopamine, and blocked by Haloperidol.ConclusionCerebral vasospasm is significantly reversed in a functional measure of vasospasm in vitro by dopamine, via a D(2)R-mediated pathway. The increase in NOS protein seen in both the endothelium and vascular smooth muscle in response to CSF(V) is enhanced by dopamine, also in a D(2)R-dependent mechanism.

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