The effect of endothelin receptor A antagonism on basilar artery endothelium-dependent relaxation after ischemic stroke

Maha Coucha, Weiguo Li, Adviye Ergul

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Aims: Endothelin (ET) receptor A antagonism decreases neuronal damage in experimental models of stroke. Since large arteries like basilar artery contribute significantly to total cerebrovascular resistance and are major determinants of microvascular pressure, dysregulation of basilar artery function may worsen stroke injury. ET-1 is involved in the regulation of basilar constriction. However, whether stroke influences vasoreactivity of basilar artery and to what extent ET-1 contributes to basilar vascular dysfunction after stroke remained unknown. The goal of this study was to test the hypothesis that ET-1 impairs basilar artery vasorelaxation after ischemia/reperfusion (I/R) injury via activation of ETA receptor. Main methods: Male Wistar rats were subjected to 3 h middle cerebral artery occlusion (MCAO) and 21 h reperfusion. One group received ETA receptor antagonist atrasentan (5 mg/kg, i.p.) at reperfusion. At 24 h, basilar arteries were isolated from control non-stroked, stroked and stroked + atrasentan-treated animals for vascular reactivity measurements using pressurized arteriograph. Key findings: Acetylcholine (Ach)-induced maximum relaxation (Rmax) was decreased in stroked animals as compared to non-stroked group and ETA antagonism partially restored it. There was also a trend for decreased EC 50 value for the antagonist treatment group indicating improved Ach sensitivity. Significance: These findings suggest that I/R not only affects vessels distal to the occlusion but also impairs relaxation of proximal large vessels. ET-1-mediated basilar artery dysfunction may contribute to neurovascular damage after stroke and early restoration of vascular function by ET receptor antagonism after I/R injury may offer a therapeutic strategy.

Original languageEnglish (US)
Pages (from-to)676-680
Number of pages5
JournalLife sciences
Volume91
Issue number13-14
DOIs
StatePublished - Oct 15 2012

Keywords

  • Atrasentan
  • Basilar artery
  • Endothelin-1
  • Ischemia/reperfusion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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