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Attenuation of experimental subarachnoid hemorrhage--induced cerebral vasospasm by the adenosine A2A receptor agonist CGS 21680.
- Source :
-
Journal of neurosurgery [J Neurosurg] 2007 Mar; Vol. 106 (3), pp. 436-41. - Publication Year :
- 2007
-
Abstract
- Object: Impaired endothelium-dependent relaxation is present in vasospastic cerebral vessels after subarachnoid hemorrhage (SAH) and may result from deficient production of endothelial nitric oxide synthase (eNOS) or increased production and/or activity of inducible NOS (iNOS). Accumulating evidence demonstrates that adenosine A2A receptors increase the production of NO by human and porcine arterial endothelial cells, which in turn leads to vasodilation. This study was designed to examine the effects of an adenosine A2A receptor agonist, (2(4-[2-carboxyethyl]phenyl)ethylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680), in the prevention of SAH-induced vasospasm.<br />Methods: . Experimental SAH was induced in Sprague-Dawley rats by injecting 0.3 ml of autologous blood into the cisterna magna of each animal. Intraperitoneal injections of CGS 21680 or vehicle were administered 5 minutes and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging measurements of cross-sectional areas of the basilar artery (BA) 48 hours after SAH. Expression of eNOS and iNOS in the BA was also evaluated. Prior to perfusion-fixation, there were no significant differences among animals in the control and treated groups in any physiological parameter that was recorded. The CGS 21680 treatment significantly attenuated SAH-induced vasospasm. Induction of iNOS mRNA and protein in the BA by the SAH was significantly diminished by administration of CGS 21680. The SAH-induced suppression of eNOS mRNA and protein was also relieved by the CGS 21680 treatment.<br />Conclusions: This is the first evidence that adenosine A2A receptor agonism is effective in preventing SAH-induced vasospasm without significant complications. The beneficial effect of adenosine A2A receptor agonists may be, at least in part, related to the prevention of augmented expression of iNOS and the preservation of normal eNOS expression following SAH. Adenosine A2A receptor agonism holds promise in the treatment of cerebral vasospasm following SAH and merits further investigation.
- Subjects :
- Adenosine therapeutic use
Animals
Disease Models, Animal
Nitric Oxide Synthase Type II genetics
Nitric Oxide Synthase Type II metabolism
Nitric Oxide Synthase Type III genetics
Nitric Oxide Synthase Type III metabolism
RNA, Messenger metabolism
Rats
Rats, Sprague-Dawley
Subarachnoid Hemorrhage enzymology
Subarachnoid Hemorrhage pathology
Adenosine analogs & derivatives
Adenosine A2 Receptor Agonists
Antihypertensive Agents therapeutic use
Phenethylamines therapeutic use
Subarachnoid Hemorrhage complications
Vasospasm, Intracranial etiology
Vasospasm, Intracranial prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3085
- Volume :
- 106
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of neurosurgery
- Publication Type :
- Academic Journal
- Accession number :
- 17367066
- Full Text :
- https://doi.org/10.3171/jns.2007.106.3.436