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UBC Theses and Dissertations

Pharmacology of the isolated mouse middle cerebral artery Ni, Bai

Abstract

Cerebral arteries play an important role in the regulation of cerebral blood flow through autoregulation to supply oxygen and nutrients for the brain and neurons. Although investigation of the activity of cerebral blood vessels has a long and distinguished history, there exists a deficit in the pharmacology of the isolated mouse cerebrovascular system. In this thesis, we designed protocols to determine whether the mouse middle cerebral artery (MCA) possessed similar properties with respect to myogenic control and responsiveness to vasoconstrictors and vasodilators. We found that the intrinsic tone of the mouse MCA was evoked at low pressures with no significant additional constriction occurring at higher pressures (>50mmHg). Inhibition of nitric oxide (NO) and endothelin-1 (ET-1) altered the extent of pressure-induced myogenic tone. Unlike the general insensitivity of cerebral arteries to adrenergic receptor stimulation in most other species, the mouse M C A constricted to ocadrenergic receptor activation. Interestingly, 5-HT and histamine, which are potent vasomotor factors, did not elicit any effect on the mouse MCA. In summary, the mouse MCA has a pharmacological profile that is distinct from other species, including humans; however, similar to findings in other cerebral arteries, the mouse MCA shows intracellular sensitization to Ca²⁺ following receptor activation. Mouse is the most commonly used species for constructing a genetically modified model to explore the intricacies of cerebrovasculature system; therefore, our study provides pertinent input for the further characterization of the pathophysiology and dysfunction in cerebral vasculature.

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