Received December 20, 2006
Revised January 31, 2007
Accepted after revision February 14, 2007

¹ Baker Heart Research Institute

^* To whom correspondence should be addressed. E-mail: dmitry.mayorov{at}baker.edu.au.

	Abstract

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 (AT1) receptor is increasingly recognised as an important regulator of cardiovascular reactivity. Given that a wide variety of AT1 receptor signalling pathways exists in neurons, 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 (O2), are important intracellular messengers of many actions of brain Ang II. In particular, studies employing microinjection of O2 scavengers directly into the rostral ventrolateral medulla (RVLM) and dorsomedial hypothalamus of rabbits have shown that the activation of AT1 receptor-O2 signalling is required for full manifestation of the cardiovascular response to emotional stress. This role of O2 appears to be highly specific because O2 scavengers in the RVLM do not alter the sympathoexcitatory response to baroreceptor unloading or sciatic nerve stimulation. The subcellular mechanisms for the stress-induced O2 production are likely to include the activation of NADPH oxidase and are essentially independent of nitric oxide. This review summarises current knowledge of redox-sensitive signalling mechanisms in the brain that regulate cardiovascular effects of stress. Additionally, it presents initial evidence that O2 may be less important in the activation of central pressor pathways mediating cardiovascular arousal associated with appetitive events such as food anticipation and feeding.

Key Words: Free radical, Rostral ventrolateral medulla, Stress