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- Title
Vasomodulatory effects of the angiotensin II type 1 receptor antagonist losartan on experimentally induced cerebral vasospasm after subarachnoid haemorrhage.
- Authors
Wanderer, Stefan; Mrosek, Jan; Gessler, Florian; Seifert, Volker; Konczalla, Juergen
- Abstract
Background: Cerebral vasospasm following subarachnoid haemorrhage (SAH) remains one of the major factors contributing to poor overall patient outcome. Prostaglandin F2-alpha (PGF2a) induces vasoconstriction. After SAH, PGF2a leads to cerebral inflammation and enhanced vasoconstriction, resulting in cerebral vasospasm. Losartan is already known to have beneficial effects in stroke models and also on several cerebral inflammatory processes. Therefore, the aim of the study was to analyse the effect of losartan on PGF2a-enhanced vasoconstriction after SAH. Methods: To investigate the effect of losartan on PGF2a-enhanced vasoconstriction after SAH, cerebral vasospasm was induced by a double-haemorrhage model. Rats were killed on day 3 and 5 after SAH followed by measurement of the isometric force of basilar artery ring segments in an organ bath. Results: PGF2a induced a dose-dependent contraction. After pre-incubation with losartan, the maximum contraction (E) for sham-operated animals was significantly lowered [E 6% in losartan 3 × 10 molar (M) vs. 56% without losartan]. Also, after induced SAH, PGF2a induced no vasoconstriction in pre-incubated vessels with losartan 3 × 10 M on day 3 (d3) as well as on day 5 (d5). For the vasorelaxative investigations, vessel segments were pre-incubated with PFG2a. Cumulative application of losartan completely resolved the pre-contraction in sham-operated animals (non SAH: 95% relaxation). After SAH, losartan not only resolved the pre-contraction (d5: 103%), but also exceeded the pre-contraction (d3: 119%). Therefore, a statistically significantly increased and earlier relaxation was calculated for all losartan concentrations [E (d3/d5) and pD (d3/d5)] compared with the solvent control group. Conclusion: In a physiological and pathophysiological setup, losartan reduces a PGF2-induced vasoconstriction and reverses a PGF2a-precontraction completely. This fact can be integrated in pushing forward further concepts trying to antagonise/prevent cerebral vasospasm after SAH.
- Subjects
ANGIOTENSIN II; CEREBRAL vasospasm; CEREBROVASCULAR disease; SPASMS; HEALTH outcome assessment; PROSTAGLANDINS
- Publication
Acta Neurochirurgica, 2018, Vol 160, Issue 2, p277
- ISSN
0001-6268
- Publication type
Article
- DOI
10.1007/s00701-017-3419-2