Dopamine D 2 -Receptor-Mediated Increase in Vascular and Endothelial NOS Activity Ameliorates Cerebral Vasospasm After S
- PDF / 521,683 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 65 Downloads / 134 Views
TRANSLATIONAL RESEARCH
Dopamine D2-Receptor-Mediated Increase in Vascular and Endothelial NOS Activity Ameliorates Cerebral Vasospasm After Subarachnoid Hemorrhage In Vitro Gail J. Pyne-Geithman Æ Danielle N. Caudell Æ Matthew Cooper Æ Joseph F. Clark Æ Lori A. Shutter
Published online: 20 September 2008 Ó Humana Press Inc. 2008
Abstract Introduction Cerebral 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. Methods Cerebrospinal fluid (CSF) from patients with cerebral vasospasm after SAH (CSFV) 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. Results Dopamine receptor 1, 2, and 3 subtypes are all present in porcine carotid artery. Dopamine significantly reversed spasm in vitro (67% relaxation), and this G. J. Pyne-Geithman (&) D. N. Caudell M. Cooper J. F. Clark L. A. Shutter Department of Neurology, University of Cincinnati, 3125 Eden Avenue, 2324 Vontz Center, Cincinnati, OH 45267-0536, USA e-mail: [email protected] L. A. Shutter Department of Neurosurgery, University of Cincinnati, Cincinnati, OH, USA L. A. Shutter The Veterans Administration Medical Center, Cincinnati, OH, USA
relaxation was prevented by Haloperidol, a D2R antagonist (10% relaxation, P < 0.05), but not by D1 or D3-receptor antagonism. Both eNOS and iNOS expression were increased significantly in response to CSFV alone, and this was significantly enhanced by addition of dopamine, and blocked by Haloperidol. Conclusion Cerebral vasospasm is significantly reversed in a functional measure of vasospasm in vitro by dopamine, via a D2R-mediated pathway. The increase in NOS protein seen in both the endothelium and vascular smooth muscle in response to CSFV is enhanced by dopamine, also in a D2R-dependent mechanism. Keywords Vasospasm Intracranial Subarachnoid hemorrhage (SAH) Dopamine Nitric oxide Nitric oxide synthase
Introduction Delayed cerebral vasospasm is a significant cause of morbidity and mortality in patients surviving an aneurysmal subarachnoid hemorrhage (SAH). Cerebral vasospasm occurs in 30–50% of all surviving SAH patients, leading to further stroke, poor recovery, neurological deficit, and often death. Interestingly, there is a delay of 3–10 days between the SAH and the onset of cerebral vasospasm [1]. Despite extensive research on the etiology of cerebral
Data Loading...
