Background: Oxidative stress is central in pathobiology of many diseases. The focus of this Thesis is on oxidative mechanisms involved in signaling through angiotensin II (Ang II)- and beta-1 adrenergic receptors (ARs), and their effects on the membrane proteins endothelial nitric oxide synthase (eNOS) and Na+-K+ pump in cardiovascular system. The redox mechanism investigated was glutathionylation, a reversible modification of cysteines, with effects on proteins similar to phosphorylation. As the final aim, we examined the effects of beta-3 AR stimulation on redox pathways and membrane proteins in diabetes.
Results and conclusions: We show that redox signaling is an intrinsic part of beta-1 AR-coupled signal transduction, and provide a novel understanding for clinical efficacy of beta-1 AR blockade. The scheme emanating from our studies elucidates pathways that maintain the nitroso-redox balance in the cardiovascular system under physiological conditions and their dysregulation under Ang II-mediated and diabetes-induced oxidative stress. We present compelling data on protective effects of beta-3 AR stimulation to override the diabetes-induced dysregulated redox processes and highlight their role in re-establishment of redox homeostasis in cardiovascular system. Our data strongly support the idea that this class of drugs can be useful in reducing the cardiovascular burden of diabetes.