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

Abstract

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 redox-sensitive 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).

Potential of protease inhibitor in 3-nitropropionic acid induced Huntington's disease like symptoms: Mitochondrial dysfunction and neurodegeneration

“…Angiotensin II stimulates vascular NADPH oxidase, which generates superoxide by transferring electrons from NADPH inside the cell across the membrane. Angiotensin II contributes to mitochondrial ROS generation not only due to its effect on cytoplasmic NADPH oxidase, but also by direct effects on the mitochondria (Nautiyal et al, 2013).…”

Molecular Mechanisms of Proteins — Targets for SARS-CоV-2 (Review)

“…Regulation of vascular tone, cell proliferation, inflammation [48] Protection of NVU cells in insulin resistance, cardiovascular and renal diseases [49,50] Reducing anxiety Modifying the production of corticotropin-releasing hormone in the hypothalamus [52] Decreasing the production of free radicals Initiation of redox signal transduction [53] Modifying the expression of tight junction proteins (claudin-5, ZO1) Reducing the expression of matrix metalloproteinase MMP-9 [54,55] Stimulation of ATP production Preventing mitochondrial fragmentation [56] AT IV Protecting brain cells from ischemia, reducing memory deficit [49,50,57,58] Inhibiting the catalytic activity of IRAP Modifying the glucose transport into cells [59] Inhibition of cysteine aminopeptidase (improving learning and memorization) Anticonvulsant and antiepileptic action Control over the cerebral vascular tone [59,60] Accumulation of endogenous oxytocin [61]…”

Molecular Basis of the Brain Renin Angiotensin System in Cardiovascular and Neurologic Disorders: Uncovering a Key Role for the Astroglial Angiotensin Type 1 Receptor AT1R

“…At a molecular level, several mechanisms such as endoplasmic reticulum stress, mitochondrial dysfunction, and redoxsensitive transcriptional factors have all been attributed to brain-derived Ang II promoting neurogenic hypertension and baroreflex impairment (Nautiyal et al, 2013;Coble et al, 2015;Young and Davisson, 2015;Case et al, 2017). An increase in reactive oxygen species (ROS) levels in the brainstem cardioregulatory centers is a crucial step by which Ang II is able to augment multiple cardiovascular parameters such as sympathetic tone, heart rate, and water intake (Zimmerman et al, 2002(Zimmerman et al, , 2004Nozoe et al, 2008;Chan and Chan, 2012).…”