Artikel
Reversal of cortical spreading ischemia induced vasoconstriction of isolated rat MCA by T-type Ca2+ channel inhibition
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Autoren
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U. Lindauer
- Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
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H. Baumgärtner
- Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
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M. Schreiber
- Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
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S. Pinkernell
- Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
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B. Meyer
- Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
| Veröffentlicht: | 4. Juni 2012 |
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Gliederung
Text
Objective: During nitric oxide synthase (NOS) inhibition, cortical spreading depolarisation (CSD) can induce severe vasoconstriction (cortical spreading ischemia, CSI) [1]. CSI can be modeled in the isolated middle cerebral artery (MCA) by application of combined extraluminal ion changes according to changes of the extracellular milieu during CSI [2]. The CSI-associated vasoconstriction can be reverted to vasodilation by L-type Ca2+ channel inhibition with nimodipine. It has recently been shown that dihydropyridine-insensitive calcium currents contribute to cerebrovascular reactivity [3]. We therefore evaluated whether T-type Ca2+ channel inhibition is capable of reverting CSI-related vasoconstriction to vasodilation.
Methods: Rats were anesthetized and decapitated. The MCA was dissected, cannulated and pressurized. Vascular reactivity to CSI induced ion changes was tested under baseline conditions and under NOS inhibition, followed by L-type channel inhibition with nimodipine or by T-type channel inhibition by mibefradil during sustained NOS inhibition.
Results: In response to CSI cocktail the arteries significantly dilated from 75 ± 12 μm to 89 ± 17 μm. During NOS inhibition by L-NNA, CSI cocktail induced vasoconstriction from 54 ± 9 μm to 46 ± 7 μm, and application of the L-type channel antagonist nimodipine (10-7 M) as well as the T-type channel inhibitor mibefradil (10-8 M) reestablished vasodilation to CSI cocktail (nimodipine: baseline: 62 ± 15 μm, CSI cocktail: 72 ± 16 μm; mibefradil: baseline: 95 ± 12 μm, CSI cocktail: 113 ± 11 μm).
Conclusions: Compared with L-type channel inhibition, T-type channel inhibition is equally capable of reverting CSI-related vasoconstriction during NOS inhibition to vasodilation. In animal models of subarachnoid hemorrhage, expression of L-type channels has been shown to be reduced, whereas T-type channels are upregulated [4]. Because T-type channels have a larger role in smaller vessels [3], it has to be further evaluated whether combined block of T and L-type channels may represent an effective approach not only to reverse cerebral vasospasm of larger vessels but also CSD induced ischemic events within the microcirculation [5].
References
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