Physiological Importance of Vascular Oxidant Signaling

PO2 Sensing

The sensing of changes in oxygen tension potentially originates in many circumstances from the PO2-dependence of the substrate requirements for oxygen utilization by oxidases that generate ROS or by oxidative enzymes that use oxygen for the formation of reactive enzyme intermediates involved in the generation of vasoactive mediators including prostaglandins, NO, and cytochrome P450. There is substantial evidence that many of these systems are key processes through which changes in PO2 regulate vascular function. It appears that ROS (e.g., H2O2) originating from the basal activity of nox-type oxidases and mitochondria are mediators of PO2-linked signaling systems that may function through the redox regulation of K+ and Ca2+ channels, and cGMP production by sGC.

Sensing of Physical Forces

Stretch and shear forces in the vessel wall have been demonstrated to promote activation of nox-type oxidases. The stretch component of increased blood pressure activates myogenic contractions through the generation of ROS and signaling systems potentially activated either directly or indirectly by ROS including protein kinase C and MAP kinases which appear to contribute to stretch-induced vascular contractile and growth-related adaptive remodeling responses. High levels of shear and stretch increase superoxide in endothelium, resulting in an attenuation of NO-mediated dilator responses.

Hormone and Growth Factor Receptor Function

Many receptors that possess growth-promoting actions in vascular tissue cause activation of nox-type oxidases and the stimulation of redox-linked signaling systems such as MAP kinases. Although many of the signaling events activated through growth-promoting receptors do not appear to be redox-mediated, ROS seem to have an important modulating role in controlling the growth response. Excessive generation of ROS will activate apoptosis-related signaling and processes associated with cell death as mitochondrial function deteriorates.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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