The Stress of Relaxation

Oxidants and free radicals, according to the vitamin mongers, are the ruination of our existence. They include super-oxides (O₂^-), hydroxyl radicals (OH^-), and peroxides (H₂O₂), collectively called "reactive oxygen species" (ROS). These molecular brigands--the by-products of mitochondrial metabolism--corrode molecules by snatching their electrons. They are blamed for causing cancer, heart disease, Alzheimer's disease, and old age (1). Yet in a reversal of the view that has dominated since the 1950s, we have come to appreciate that ROS play essential roles in healthy cell signaling. On page 1393 in this issue, Burgoyne et al. (2) show that oxidation activates a key enzyme that causes blood vessels to relax. This finding raises a paradox: Why, if oxidation can relax blood vessels, is oxidative stress associated with hypertension?

Vascular smooth muscle cells contract using filaments of actin and myosin molecules. Hormones and neurotransmitters control muscle tone by affecting the phosphorylation state of myosin (see the figure) (3, 4). Vasoconstrictors, such as angiotensin II, increase the concentration of cytosolic calcium ions (Ca²⁺), which activates an enzyme (myosin light chain kinase) that phosphorylates myosin. Also, an enzyme (myosin light chain phosphatase) that dephosphorylates myosin is inhibited. Vasorelaxants, such as acetylcholine, have the opposite effects. Protein kinase G (PKG) is a pivotal enzyme in vasorelaxation (3). The PKGI isoform studied by Burgoyne et al. phosphorylates a panoply of substrates, ultimately decreasing myosin phosphorylation.

whole story