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Neurocritical Care

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01.04.2009 | Translational Research

Dopamine D₂-Receptor-Mediated Increase in Vascular and Endothelial NOS Activity Ameliorates Cerebral Vasospasm After Subarachnoid Hemorrhage In Vitro

verfasst von: Gail J. Pyne-Geithman, Danielle N. Caudell, Matthew Cooper, Joseph F. Clark, Lori A. Shutter

Erschienen in: Neurocritical Care | Ausgabe 2/2009

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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 (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.

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 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 CSF_V 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 CSF_V is enhanced by dopamine, also in a D₂R-dependent mechanism.

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Titel: Dopamine D2-Receptor-Mediated Increase in Vascular and Endothelial NOS Activity Ameliorates Cerebral Vasospasm After Subarachnoid Hemorrhage In Vitro
verfasst von: Gail J. Pyne-Geithman
Danielle N. Caudell
Matthew Cooper
Joseph F. Clark
Lori A. Shutter
Publikationsdatum: 01.04.2009
Verlag: Humana Press Inc
Erschienen in: Neurocritical Care / Ausgabe 2/2009
Print ISSN: 1541-6933
Elektronische ISSN: 1556-0961
DOI: https://doi.org/10.1007/s12028-008-9143-2

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Introduction

Methods

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