• Chun-Po Yen, Shih-Chieh Chen, Tze-Kan Lin, Shu-Chuan Wu, Chao-Yuah Chang, Sheng-I Lue, Arco Y Jeng, Neal F Kassell, and Aij-Lie Kwan.
• Department of Neurosurgery, Kaohsiung Medical University, Kaohsiung, Taiwan.
• J. Cardiovasc. Pharmacol. 2004 Nov 1;44 Suppl 1:S474-8.

AbstractPrevious studies indicate that intravenous infusion of CGS 26303, an endothelin-converting enzyme inhibitor, prevents and reverses cerebral vasospasm after experimental subarachnoid hemorrhage. Attenuation of the vasospastic response could result from enhanced production of nitric oxide via activation of endothelial nitric oxide synthase, neuronal nitric oxide synthase, or inducible nitric oxide synthase in brain tissue. Carbon monoxide has the same attenuation effect and is synthesized by inducible heme-oxygenase- 1 or constitutive heme-oxygenase-2. In this study, we investigated the effect of endothelin-converting enzyme inhibitor on mRNA expression of endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase, heme-oxygenase- 1 and heme-oxygenase-2 in brain tissue of rats subjected to subarachnoid hemorrhage using semi-quantitative reverse transcription-polymerase chain reaction. The results showed that gene expression of inducible nitric oxide synthase or HSP70 was not detected in all groups of rats (n = 5/group). Expression of endothelial nitric oxide synthase, neuronal nitric oxide synthase or heme-oxygenase-2 mRNA in brain tissue in the groups of subarachnoid hemorrhage or subarachnoid hemorrhage treated with endothelin-converting enzyme inhibitor appeared to be the same as compared with control rats. The subarachnoid hemorrhage rats treated with endothelin-converting enzyme inhibitor showed a significant increase in the levels of heme-oxygenase-1 mRNA expression as compared with both subarachnoid hemorrhage and control rats. These data suggest that the reduction of cerebral vasospasm by CGS 26303 in rats subjected to experimental subarachnoid hemorrhage may result from both over-expression of heme-oxygenase-1 in brain tissue and suppression of endothelin biosynthesis in basilar arteries.

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