Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions.

Jaspreet Kalra,Atish Prakash,Abu Bakar Abdul Majeed,Puneet Kumar

doi:10.1177/1470320315583582

Abstract

Work on the brain renin-angiotensin system has been explored by various researchers and has led to elucidation of its basic physiologies and behavior, including its role in reabsorption and uptake of body fluid, blood pressure maintenance with angiotensin II being its prominent effector. Currently, this system has been implicated for its newly established effects, which are far beyond its cardio-renal effects accounting for maintenance of cerebral blood flow and cerebroprotection, seizure, in the etiology of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and bipolar disorder. In this review, we have discussed the distribution of angiotensin receptor subtypes in the central nervous system (CNS) together with enzymatic pathways leading to active angiotensin ligands and its interaction with angiotensin receptor 2 (AT2) and Mas receptors. Secondly, the use of angiotensin analogues (angiotensin converting enzyme inhibitors and AT1 and/or AT2 receptor blockers) in the treatment and management of the CNS disorders mentioned above has been discussed.

Highlights

Existence of the brain renin–angiotensin system (RAS)/ local RAS, despite its presence at the periphery, is claimed and confirmed by several studies.[1,2] These preliminary findings provided a boon and encouraged a number of investigators all over the world to scratch their heads to carry out their work on this proposed brain system
Results of this study demonstrated that angiotensin converting enzyme (ACE) inhibitors had shown significant increase in both antioxidant enzyme levels, i.e. superoxide dismutase (SOD) and glutathione peroxidase, and depleted the levels of reactive oxygen species by reducing the levels of oxidative stress markers
In this review we have discussed the disease states associated with the modulations in RAS, primarily those focusing on ACE inhibitors, Angiotensin receptor blockers (ARBs), antagonists, and their therapeutic approaches

Summary

Introduction

Existence of the brain renin–angiotensin system (RAS)/ local RAS, despite its presence at the periphery, is claimed and confirmed by several studies.[1,2] These preliminary findings provided a boon and encouraged a number of investigators all over the world to scratch their heads to carry out their work on this proposed brain system.

Results

Conclusion