ABSTRACT
Focal adhesion kinase (FAK) is a broadly expressed tyrosine kinase implicated in cellular functions such as migration, growth and survival. Emerging data support a role for FAK in cardiac development, reactive hypertrophy and failure. Data reviewed here indicate that FAK plays a critical role at the cellular level in the responses of cardiomyocytes and cardiac fibroblasts to biomechanical stress and to hypertrophic agonists such as angiotensin II and endothelin. The signaling mechanisms regulated by FAK are discussed to provide insight into its role in the pathophysiology of cardiac hypertrophy and failure.
Subject(s)
Animals , Humans , Cardiomegaly/enzymology , Fibroblasts/enzymology , Focal Adhesion Protein-Tyrosine Kinases/physiology , Heart Failure/enzymology , Myocytes, Cardiac/enzymology , Cell Proliferation , Cardiomegaly/etiology , Cardiomegaly/physiopathology , Heart Failure/etiology , Heart Failure/physiopathology , Signal Transduction/physiologyABSTRACT
The bradycardia that occurs in response to vagal stimulation or to methacholine after 6 h of sinoaort denervation (SAD) was studied in SAD rats before and agter adrenergic blockade to determinewhether the peripheral vagal action was impaired by sympathetic hyperactivity. A marked attenuation in the response to methacholine and no difference in the responses to vagal stimulation were observed in SAD rats compared to sham-operated controls. The adrenergic blockade attenuated the responses to both vagal stimulation and nethacholine in control rats but not in SAD rats. These finding revealed an impairment of peripheral vagal function after 6 h of SAD, probaly due to a decreased sensitivity of the muscarinic receptors