Renin-angiotensin system blockade attenuates brain mitochondrial dysfunction, oxidative stress, and neuroinflammation associated with hypertension, metabolic disorders, and aging

Your competent? doctor created protocols on this years ago, right? Oh NO! YOUR DOCTOR, HOSPITAL AND BOARD OF DIRECTORS ARE ALL COMPPLETELY INCOMPETENT!     

So, they actually prefer wallowing in their ignorance, doesn't require as much brainpower!

renin angiotensin system (2 posts to October 2016)

 Renin-angiotensin system blockade attenuates brain mitochondrial dysfunction, oxidative stress, and neuroinflammation associated with hypertension, metabolic disorders, and aging

 Sebastián García Menéndez, Felipe Inserra, Elena MV de Cavanagh, Leon Ferder, Walter Manucha Sebastián García Menéndez, Department of Pathology, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina Felipe Inserra, Department of Postgraduate, Austral University, Pilar 1630, Argentina Elena MV de Cavanagh, Department of Postgraduate, Austral University Hospital, Arterial Hypertens Ctr, Sch Biomed Sci, CABA 1629, Argentina Leon Ferder, Department of Pharmacology, Universidad Maimónides, Ciudad Autónoma de Buenos Aires C1405, Argentina Walter Manucha, Department of Pathology, Institute of Medicine and Experimental Biology of Cuyo, National Council for Scientific and Technological Research, National University of Cuyo, Laboratory of Basic and Translational Experimental Pharmacology, Faculty of Medical Sciences, Mendoza 5500, Argentina ORCID number: Walter Manucha (0000-0002-2279-7626). Author contributions: García Menéndez S, Inserra F, de Cavanagh EMV, Ferder L and Manucha W were responsible for writing, discussion and preparation of this manuscript, and have also read and approved the final version of the manuscript. Conflict-of-interest statement: The authors declare that they have no conflict of interest. Corresponding author: Walter Manucha, PhD, Professor, Department of Pathology, Institute of Medicine and Experimental Biology of Cuyo, National Council for Scientific and Technological Research, National University of Cuyo, Laboratory of Basic and Translational Experimental Pharmacology, Faculty of Medical Sciences, Avenue El Libertador 80, Mendoza 5500, Argentina. wmanucha@yahoo.com.ar Received: August 20, 2025 Revised: October 25, 2025 Accepted: January 20, 2026 Published online: March 20, 2026 Processing time: 207 Days and 13.6 Hours 

 Abstract 

Although aging is an inherent part of life, it represents a process of progressive dysfunction rather than a fixed biological outcome. Consequently, highly prevalent conditions such as cardiorenal-metabolic syndrome-which encompasses obesity, hypertension (HTN), and metabolic disorders-can accelerate age-related changes. The renin-angiotensin system (RAS) plays a critical role in pathophysiology and affects multiple organs, including the brain. The central nervous system contains both RAS branches: The ACE/Ang II/AT1 and AT2 receptor axis, as well as the ACE2/Ang-(1-7)/Mas receptor axis. Neuroinflammation is a chronic process characterized by glial cell activation triggered by increased production of reactive oxygen and nitrogen species, resulting in oxidative stress. Mitochondria are the primary cellular sites where these processes occur. Under conditions such as metabolic disorders, obesity, HTN, and aging, these reactions are markedly accelerated. Associated mechanisms include insulin resistance, elevated levels of advanced glycation end-products, and disruption of the blood-brain barrier. The consequences of these alterations may include brain dysfunction, cognitive decline, Parkinson’s disease, and neurodegenerative conditions such as Alzheimer’s disease. This review focuses on the primary effects of therapeutic interventions on mitochondrial function, with particular attention to the modulation of oxidative stress, chronic neuroinflammation, and glial dysregulation. We highlight the strategic use of angiotensin receptor blockers and ACE2 activators as promising tools that may redefine the prevention and treatment of vascular dementia and other neurodegenerative diseases of inflammatory origin. 

 Key Words: Renin-angiotensin system blockade; Oxidative stress; Central nervous system inflammation; Neurodegeneration; Hypertension; Metabolic disorders; Mitochondria; Aging Core Tip: This study highlights renin-angiotensin system blockade as a promising strategy for preventing brain damage associated with hypertension, metabolic disorders, and aging. These conditions accelerate mitochondrial dysfunction, oxidative stress, and neuroinflammation. Our work focuses on the strategic use of angiotensin receptor blockers and ACE2 activators, demonstrating their potential to mitigate these pathological processes and offering a novel avenue for the prevention and treatment of vascular dementia and other neurodegenerative diseases. Citation: García Menéndez S, Inserra F, de Cavanagh EM, Ferder L, Manucha W. Renin-angiotensin system blockade attenuates brain mitochondrial dysfunction, oxidative stress, and neuroinflammation associated with hypertension, metabolic disorders, and aging. World J Exp Med 2026; 16(1): 113259 URL: https://www.wjgnet.com/2220-315x/full/v16/i1/113259.htm DOI: https://dx.doi.org/10.5493/wjem.v16.i1.113259

García Menéndez S, Inserra F, de Cavanagh EM, Ferder L, Manucha W. Renin-angiotensin system blockade attenuates brain mitochondrial dysfunction, oxidative stress, and neuroinflammation associated with hypertension, metabolic disorders, and aging. World J Exp Med 2026; 16(1): 113259 [DOI: 10.5493/wjem.v16.i1.113259]

Angiotensin II Receptor Blockers May Reduce Age-Related Cognitive Decline

Any followup at all to see if this might help stroke cognitive decline? Or will nothing occur because we have NO STROKE LEADERSHIP?  

Angiotensin II Receptor Blockers May Reduce Age-Related Cognitive Decline

By Thomas S. May
FLORENCE, Italy -- April 5, 2017 -- Individuals treated with angiotensin II receptor blockers (ARBs), including losartan, valsartan, and candesartan, experience a decreased risk for age-related cognitive decline and dementia, according to results of a cross-sectional analysis presented at the 25th European Congress of Psychiatry (EPA).
Lead author Dominik Wincewicz, MD, Medical University of Bialystok, Bialystok, Poland and colleagues observed a significant decrease in the risk for cognitive decline in subjects who received ARB treatment over the course of approximately 9 years of follow up (odds ratio [OR] = 0.445, 95% confidence interval [CI] = 0.22 to 0.90, P = .024). The risk of dementia also was decreased significantly in participants treated with ARBs (hazard ratio [HR] = 0.621, 95% CI = 0.40 to 0.98, P = .038), added Dr. Wincewicz, speaking here on April 2.
He and his fellow investigators analysed data from the population-based, longitudinal Kuopio Ischemic Heart Disease (KIHD) Risk Factor Study, an extensive epidemiologic research project launched in the 1980s, which initially involved nearly 3,000 middle-aged men from the Kuopio region in Eastern Finland. A decade later, over 1,000 women of the same age were recruited to the study. A major part of the original cohorts have been re-examined 4, 11, and 20 years after the baseline.
The researchers included a total of 1,774 subjects (920 females; baseline age range: 42 to 61 years). They utilised a cut-off score of ≥ 2 point decrease in the Mini-Mental-State Examination over a 9-year follow-up period to detect age-related cognitive decline, and a hospital discharge diagnosis of dementia as the outcome variable for dementia.
Using logistic regression, the investigators determined cross-sectional relationships, and conducted prospective analyses with the Cox proportional hazards model. The team adjusted analyses for all relevant background variables.
ARBs modulate the brain renin-angiotensin system (RAS), and have been shown to improve cognitive functioning in animal models of neuropsychiatric disorders. The brain RAS also has been considered as a new target for the treatment of Alzheimer’s Disease.
[Preserved Cognition and Reduced Age Related Cognitive Decline During Treatment with Angiotensin II Receptor Blockers: a 20-year Follow-up Study. Abstract ED773]

Therapeutic potential of the renin angiotensin system in ischaemic stroke

There really is no point in doing any stroke research. None ever seems to be followed up to create stroke protocols. Let's just save the money and continue to let our stroke survivors deal with this by themselves. Would following this fix the Capillaries that don't open due to pericytes?
http://etsmjournal.biomedcentral.com/articles/10.1186/s13231-016-0022-1

• Mariana Moreira Coutinho Arroja,
• Emma Reid and
• Christopher McCabeEmail authorView ORCID ID profile

Experimental & Translational Stroke Medicine20168:8

DOI: 10.1186/s13231-016-0022-1

©  The Author(s) 2016

Received: 22 July 2016

Accepted: 29 September 2016

Published: 7 October 2016

Abstract

The renin angiotensin system (RAS) consists of the systemic hormone system, critically involved in regulation and homeostasis of normal physiological functions [i.e. blood pressure (BP), blood volume regulation], and an independent brain RAS, which is involved in the regulation of many functions such as memory, central control of BP and metabolic functions. In general terms, the RAS consists of two opposing axes; the ‘classical axis’ mediated primarily by Angiotensin II (Ang II), and the ‘alternative axis’ mediated mainly by Angiotensin-(1–7) (Ang-(1–7)). An imbalance of these two opposing axes is thought to exist between genders and is thought to contribute to the pathology of cardiovascular conditions such as hypertension, a stroke co-morbidity. Ischaemic stroke pathophysiology has been shown to be influenced by components of the RAS with specific RAS receptor antagonists and agonists improving outcome in experimental models of stroke. Manipulation of the two opposing axes following acute ischaemic stroke may provide an opportunity for protection of the neurovascular unit, particularly in the presence of pre-existing co-morbidities where the balance may be shifted. In the present review we will give an overview of the experimental stroke studies that have investigated pharmacological interventions of the RAS.

Keywords

Acute ischaemic stroke (AIS) Renin angiotensin system (RAS) Angiotensin II (Ang II) Angiotensin-(1–7) (Ang-(1–7)) AT₁R blockers AT₂R agonists MasR agonists

Background

In the UK, stroke is the fourth leading cause of death and one of the largest contributors towards long-term disability, affecting approximately 152,000 people every year (https://www.stroke.org.uk; State of the Nation 2015) [1]. In the past 40 years the number of stroke fatalities has been decreasing, however, it is estimated that over two-thirds of stroke survivors require daily medical care and over half are left disabled [2], resulting in an annual cost of nearly £4 billion and accounting for approximately 4–6 % of total NHS expenditure [3].

Recombinant tissue plasminogen activator (rt-PA; Alteplase), is the only thrombolytic treatment currently available for acute ischaemic stroke (AIS). It acts by breaking down the clot or thrombus obstructing the cerebral vessel, thus, re-establishing blood flow. However, it has a narrow therapeutic time window of 4.5 h from stroke onset, resulting in only 2–5 % of ischaemic strokes being treated globally, and can have detrimental side effects, including haemorrhage [4]. Recent results from a number of randomised clinical trials of mechanical thrombectomy have demonstrated efficacy for this intervention up to 6 h after stroke onset [5]. The positive results from these trials have reinvigorated the stroke community and open up new possibilities for adjunctive protective strategies.

Failure to translate effective therapeutic strategies from the ‘bench to bedside’ may partly be attributed to the use of animal models that do not incorporate non-modifiable risk factors such as gender and many of the stroke co-morbidities observed in the clinical stroke population, such as hypertension, diabetes, obesity, etc. For instance, hypertension is the single most important modifiable risk factor for stroke, acting as a contributing factor in over 75 % of first time stroke patients [6] with hypertension during acute stroke is associated with poorer clinical outcome [7].

The renin angiotensin system (RAS), a peptide hormone system intrinsically involved in blood pressure regulation and blood volume homeostasis in the circulation, has been shown to be present as a local paracrine system in the brain [8]. The RAS is reported to be involved in the pathology of AIS and its risk factors [8, 9], therefore, emerging as a potential therapeutic target. This review discusses the therapeutic potential of the RAS following AIS, emphasising the importance of cerebral RAS receptor targeting and its relevance in the presence of known stroke risk factors.

Brain RAS: classical and alternative axis

In the circulation, a drop in blood pressure (systemic hypotension) and/or blood volume results in juxtaglomerular cells within the kidneys to release renin (protease) whereas increased blood pressure (hypertension) inhibits renin release under normal circumstances. Circulating angiotensinogen is hydrolysed by renin to produce Angiotensin I (Ang I), which is then further converted by angiotensin converting enzyme (ACE) to generate biological active octapeptide, Ang II (Fig. 1). Ang II, a potent vasoconstrictor, acts by stimulating Ang II type 1 and type 2 receptors (AT₁R and AT₂R) [10]. Ang II exhibits a higher affinity to the widely expressed AT₁R whereby it exerts its main physiological effects by constricting blood vessels, increasing BP, and stimulating aldosterone release from adrenal glands, promoting water and salt reabsorption in the kidneys, thus, raising blood volume levels [10]. In the last decade, an ‘alternative axis’ has been identified involving the monocarboxypeptidase, ACE2, the biologically active peptide Ang-(1–7) and its G-protein coupled receptor, Mas (MasR). Ang-(1–7) is formed by the direct actions of ACE2 on Ang II or via ACE2 induced cleavage of Ang I, generating the nine amino acid peptide Ang-(1–9), which is further converted to Ang (1–7) by ACE or peptidases such as neprilysin (NEP) [8].