The Brain Renin-Angiotensin System and Mitochondrial unction Influence on Blood Pressure and Baroreflex in Transgenic Rat Strains

Mitochondrial dysfunction is implicated in many cardiovascular diseases, including hypertension, and may be associated with an overactive renin-angiotensin system (RAS). Angiotensin (Ang) II, a potent vasoconstrictor hormone of the RAS, also impairs baroreflex and mitochondrial function. Most deleterious cardiovascular actions of Ang II are thought to be mediated by NADPH-oxidase- (NOX-) derived reactive oxygen species (ROS) that may also stimulate mitochondrial oxidant release and alter redoxsensitive signaling pathways in the brain. Within the RAS, the actions of Ang II are counterbalanced by Ang-(1-7), a vasodilatory peptide known to mitigate against increased oxidant stress. A balance between Ang II and Ang-(1-7) within the brain dorsal medulla contributes to maintenance of normal blood pressure and proper functioning of the arterial baroreceptor reflex for control of heart rate. We propose that Ang-(1-7) may negatively regulate the redox signaling pathways activated by Ang II to maintain normal blood pressure, baroreflex, and mitochondrial function through attenuating ROS (NOX-generated and/or mitochondrial).