Brain superoxide as a key regulator of the cardiovascular response to emotional stress in rabbits.
Cardiovascular reactivity, an abrupt increase in blood pressure and heart rate in response to emotional stress, is a risk factor for hypertension and heart disease. Brain angiotensin II (Ang II) type 1 (AT(1)) receptor is increasingly recognized as an important regulator of cardiovascular reactivity. Given that a wide variety of AT(1) receptor signalling pathways exists in neurones, the precise molecular mechanisms that underlie central cardiovascular actions of Ang II during emotional stress are yet to be determined. Growing evidence, however, indicates that reactive oxygen species, and in particular superoxide (.O(2)(-)), are important intracellular messengers of many actions of brain Ang II. In particular, studies employing microinjection of .O(2)(-) scavengers directly into the rostral ventrolateral medulla (RVLM) and dorsomedial hypothalamus of rabbits have shown that the activation of AT(1) receptor-.O(2)(-) signalling is required for full manifestation of the cardiovascular response to emotional stress. This role of .O(2)(-) appears to be highly specific, because .O(2)(-) scavengers in the RVLM do not alter the sympathoexcitatory response to baroreceptor unloading or sciatic nerve stimulation. The subcellular mechanisms for the stress-induced .O(2)(-) production are likely to include the activation of NADPH oxidase and are essentially independent of nitric oxide. This review summarizes current knowledge of redox-sensitive signalling mechanisms in the brain that regulate cardiovascular effects of stress. Additionally, it presents initial evidence that .O(2)(-) may be less important in the activation of central pressor pathways mediating cardiovascular arousal associated with appetitive events, such as food anticipation and feeding.
Mayorov
Dmitry N
DN
Baker Heart Research Institute, PO Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia. dmitry.mayorov@baker.edu.au
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002319:Cardiovascular System / Q000503:physiopathology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism*
D044140:Receptor, Angiotensin, Type 1; D013481:Superoxides; D020929:Mitogen-Activated Protein Kinase Kinases