Abstract 355: β-Adrenergic Stimulation Impact on Cerebrovascular Contractility Through Actin Cytoskeleton Disorganization in Rabbits

Abstract

Beta-adrenoceptor stimulations have been well-known to initiate cardiac hypertrophy accompanied by extracellular remodeling that predisposes heart failure and cardiac dysarrhythmia. However, less is known concerning cerebrovascular dysfunction induced by beta-adrenergic stimulation. We investigated whether cerebrovascular functions and related biochemical signal pathways were altered during beta-adrenergic stimulations in rabbits.

New Zealand white rabbits have been injected with isoproterenol (ISO, 0.3 mg/kg/day) for 7 days. We have studied the alteration of protein expression in cerebral arteries (CAs) using 2DE proteomics and western blot analysis and further analyzed those data using bioinformatics software. Reactive oxygen species generation and followed DNA damage were assessed deteriorative effect of ISO on CAs. Vasocontractility response to angiotensin II (Ang II) and related biochemical signal pathways were assessed to evaluate functional alteration of CAs.

Proteomic analysis revealed remarkably decreased expression of cytoskeleton organizing proteins, (e.g. actin related protein 1A and 2, α-actin, capping protein Z beta, and vimentin) and anti-oxidative stress proteins (e.g. heat shock protein 9A and stress-induced-phosphoprotein 1) in ISO-stimulated CAs. As a cause of dysregulation of actin cytoskeleton organization, we found decreased level of RhoA/ROCK1, major regulators of actin cytoskeleton organization. As functional consequences of proteomic alteration, we found the decreased transient Ca²⁺ efflux and contraction response to Ang II and high K⁺ in ISO-stimulated CAs.

We suggested that ISO stimulations reduced RhoA/ROCK activities and modified key actin based cytoskeletal and antioxidative proteins in CAs, which consequently lead to impair cerebrovascular contractility response to Ang II in rabbits.