Artikel
Role of Vasopressin-V1a-receptors for the Activation of the Cushing response
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Autoren
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K. Hockel
- Institut für Chirurgische Forschung, Klinikum der Universität München, Campus Großhadern, München; Neurochirurgische Universitätsklinik, Universitätsklinikum Tübingen
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K. Schöller
- Institut für Chirurgische Forschung, Klinikum der Universität München, Campus Großhadern, München; Neurochirurgische Klinik, Klinikum der Universität München, Campus Großhadern, München
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R. Trabold
- Institut für Chirurgische Forschung, Klinikum der Universität München, Campus Großhadern, München; Neurochirurgische Klinik, Klinikum der Universität München, Campus Großhadern, München
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N. Plesnila
- Institut für Chirurgische Forschung, Klinikum der Universität München, Campus Großhadern, München; Institut für Schlaganfall- und Demenzforschung, Klinikum der Universität München, Campus Großhadern, München
| Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: In a previous experimental study on the role of Vasopressin (AVP) for the development of early brain injury following subarachnoid hemorrhage (SAH), rats under pharmacological Vasopressin-V1a-receptor inhibition failed to exhibit postictal compensatory arterial hypertension. The aim of the present study was to further elucidate the role of AVP and its V1a-receptors as mediators for the increase in arterial blood pressure (MABP) following acutely raised intracranial pressure (ICP), i.e. the Cushing response.
Methods: In ventilated Sprague-Dawley rats, SAH was induced by endovascular perforation and the spontaneous courses of ICP and MABP were monitored at high temporal resolution (n = 10). In a second series, ICP was raised to 35 or 75 mmHg for 1 minute by inflation of an epidurally placed balloon-microcatheter. MABP was monitored continuously and plasma AVP concentration was assessed at 3 and 30 minutes (n = 6). Subsequently, the rats received either a selective Vasopressin-V1a-receptor antagonist (V1880) or vehicle (0.9% NaCl) intravenously prior to balloon inflation or SAH, while ICP and MABP were monitored continuously (n = 10, 5).
Results: Both in SAH as well as in balloon-induced intracranial hypertension, MABP was increased by 30–40 mmHg for approximately 20 minutes (p < 0.05) and plasma AVP concentration simultaneously increased 35–40-fold (p < 0.05) within 3 minutes. By inhibition of systemic V1a-receptors, postictal arterial hypertension, i.e. the Cushing response, was almost completely suppressed (p < 0.05). In rats subjected to SAH, the preemptive treatment with a V1a-receptor antagonist reduced the rate of secondary rebleedings from 30 to 0%; the mortality rate was reduced from 50 to 20%.
Conclusions: The presented data show for the first time that the ICP-induced increase in MABP, the Cushing response, is greatly dependent on acutely released AVP and is mediated via V1a-receptors. The inhibition of these peripheral V1a-receptors prevents posthemorrhagic arterial hypertension, thus reducing the incidence of secondary bleeding events and improving the outcome following SAH. V1a-receptor antagonists could be a novel and safe therapeutic principle in the treatment of SAH.
