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The effect of an adenosine A1 receptor agonist in the treatment of experimental subarachnoid hemorrhage-induced cerebrovasospasm

  • Experimental Research
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Summary

Background. Adenosine is a potent vasodilator and an important modulator of cardiovascular function. It has been postulated that nitric oxide (NO) is involved in adenosine-induced vasodilation. This study was designed to examine the effect of an adenosine A1 agonist, N6-cyclopentyladenosine (CPA), in the prevention of subarachnoid haemorrhage (SAH)-induced vasospasm.

Method. Experimental SAH was induced in Sprague-Dawley rats by injecting 0.3 mL autogenous blood into the cisterna magna. Intraperitoneal injections of CPA (0.003 mg/kg), or vehicle were administered 5 min and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging the cross sectional areas of the basilar artery 2 days after SAH. Expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in basilar artery were evaluated.

Findings. There were no significant differences among the control and treated groups in physiological parameters recorded before sacrifice. When compared with animals in the control group, cross-sectional area of basilar arteries areas in the SAH only, SAH plus vehicle and SAH plus CPA groups were reduced by 19% (p < 0.01), 22% (p < 0.01), and 9% (p = 0.133), respectively. The cross-sectional areas of the CPA-treated group differed significantly from those of the SAH only and SAH plus vehicle group (p < 0.05). Induction of iNOS-mRNA and protein in basilar artery by SAH was not significantly diminished by CPA. The SAH-induced suppression of eNOS-mRNA and protein were relieved by CPA treatment.

Conclusions. This is the first evidence to show an adenosine A1 receptor agonist is effective in partially preventing SAH-induced vasospasm without significant cardiovascular complications. The mechanisms of adenosine A1 receptor agonists in attenuating SAH-induced vasospasm may be, in part, related to preserve the normal eNOS expression after SAH. Inability in reversing the increased iNOS expression after SAH may lead to the incomplete anti-spastic effect of CPA.

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Authors and Affiliations

  1. Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    C. L. Lin, Y. F. Su, A. S. Lieu, S. L. Howng & A. L. Kwan

  2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    C. L. Lin, Y. F. Su, H. C. Shih & A. S. Lieu

  3. Departments of Neuroscience and Neurological Surgery, University of Virginia Health System, Charlottesville, VA, USA

    A. S. Dumont & K. S. Lee

  4. School of Nursing, Mei-Ho Institute of Technology, Pintung, Taiwan

    H. C. Shih

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  1. C. L. Lin
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Lin, C., Su, Y., Dumont, A. et al. The effect of an adenosine A1 receptor agonist in the treatment of experimental subarachnoid hemorrhage-induced cerebrovasospasm. Acta Neurochir (Wien) 148, 873–879 (2006). https://doi.org/10.1007/s00701-006-0793-6

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