Anti-stress and nootropic activity of drugs affecting the renin-angiotensin system in rats based on indirect biochemical evidence

Abstract

The present study provides scientific support for the anti-stress and nootropic activities of aliskiren, valsartan and their combination.

Within the Brain: The Renin Angiotensin System

“…Blocking the AT1R by valsartan resulted in improvement in forced-swim stress and scopolamine-induced amnesia [ 95 ]. The anti-stress effect was associated with a decrease in urinary metabolites of stress-associated precursor molecules such as noradrenaline and cortisone, while the nootropic effect (enhancing learning and memory) was associated with increased acetylcholine through a decrease in acetylcholinesterase activity [ 95 ].…”

“…Blocking the AT1R by valsartan resulted in improvement in forced-swim stress and scopolamine-induced amnesia [ 95 ]. The anti-stress effect was associated with a decrease in urinary metabolites of stress-associated precursor molecules such as noradrenaline and cortisone, while the nootropic effect (enhancing learning and memory) was associated with increased acetylcholine through a decrease in acetylcholinesterase activity [ 95 ]. In fact, the improvement in memory and learning by valsartan could also be mediated in part through their anti-stress effects because exposure to chronic stress and glucocorticoid administration impairs cognition [ 95 , 96 ].…”

“…Yet, ICV injection ameliorated brain damage and cognitive deficits by augmenting the signaling induced by the Ang II/AT1 axis in a model of subcortical vascular dementia induced by bilateral common carotid artery stenosis [ 11 ]. Aliskiren also resulted in improvement in forced-swim stress and scopolamine-induced amnesia alone and in combination with valsartan [ 95 ]. This was associated with a decrease in urinary metabolites of stress-associated precursor molecules and increased acetylcholine through a decrease in acetylcholinesterase activity [ 95 ].…”

“…Aliskiren also resulted in improvement in forced-swim stress and scopolamine-induced amnesia alone and in combination with valsartan [ 95 ]. This was associated with a decrease in urinary metabolites of stress-associated precursor molecules and increased acetylcholine through a decrease in acetylcholinesterase activity [ 95 ].…”

Hydration and beyond: neuropeptides as mediators of hydromineral balance, anxiety and stress-responsiveness

“…The RAAS has gained considerable attention over the past decade as a potential therapeutic target for treating stress-related disorders, anxiety, depression, alcoholism, cognitive impairment as well as neuroinflammatory and neurodegenerative diseases (Saavedra and Pavel, 2005 ; Albrecht, 2010 ; Saavedra, 2012 ; Anil Kumar et al, 2014 ). Angiotensin receptor blockers administered either peripherally or centrally, improve mood and cognition as well as attenuate HPA axis and sympathetic responses to stressors having strong psychogenic components (Saavedra and Pavel, 2005 ; Albrecht, 2010 ; Saavedra, 2012 ; Anil Kumar et al, 2014 ). While the specific circuits that angiotensin receptor antagonists modulate to achieve these affects are not fully understood, increased circulating Ang-II is known to influence hypothalamic function through various pathways including those originating in CVOs and regions governing mood and affect.…”