Nebivolol attenuates cerebral vasospasm both by increasing endothelial nitric oxide and by decreasing oxidative stress in an experimental subarachnoid haemorrhage.
OBJECTIVE
Evidence suggests that reduction of nitric oxide (NO) bioavailability due to oxidative stress plays a central role in the pathophysiology of cerebral vasospasm after subarachnoid haemorrhage (SAH). To prevent SAH-induced cerebral vasospasm, therefore we used nebivolol hydrochloride as a NO-mediated vasodilator and an antioxidant drug in an experimental rat model of SAH.


METHODS
Forty female Wistar rats were divided into control, SAH, SAH plus placebo, and SAH plus nebivolol groups. Starting six hours after inducing SAH, 5 mg/kg of nebivolol hydrochloride and of pharmaceutical excipients of nebivolol was given orally once daily for five days to SAH plus nebivolol and SAH plus placebo groups, respectively. The lumen diameter and vessel wall thickness of the basilar artery were measured in brain sections. The serum and brain supernatant levels of nitric oxide (NO) were analysed. The brain supernatant levels of intrinsic antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as markers of the antioxidant status.


RESULTS
Nebivolol administration attenuated cerebral vasospasm both by increasing NO levels and by decreasing oxidative stress. Our study also demonstrated that nebivolol administration reverses SAH created imbalance between SOD and GSH-Px by increasing GSH-Px activity relative to SOD.


CONCLUSIONS
Nebivolol attenuates the cerebral vasospasm after SAH both increasing NO levels and decreasing oxidative stress. Therefore, it may promise to prevent SAH-induced cerebral vasospasm as an anti-spasmodic and anti-oxidant agent.
a Department of Neurosurgery , Inonu University School of Medicine , Malatya , Turkey.
Mehmet Arif
MA
Aladag
b Department of Biochemistry , Inonu University School of Medicine , Malatya , Turkey.
Yusuf
Y
Turkoz
c Department of Pharmacology , Inonu University School of Medicine , Malatya , Turkey.
Hakan
H
Parlakpinar
d Department of Histology , Inonu University School of Medicine , Malatya , Turkey.
Mehmet
M
Gul
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D062186:Arterial Pressure / Q000187:drug effects; D001488:Basilar Artery / Q000473:pathology; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D000068577:Nebivolol / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010276:Parasympatholytics / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D010276:Parasympatholytics; D000068577:Nebivolol; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
NO; SAH; cerebral vasospasm; nebivolol; oxidative stress