The intranasal administration of hypertension drugs perindopril and captopril confers neuroprotection for the brains of animals with Alzheimer’s disease.
Angiotensin-converting enzyme (ACE) converts angiotensin I into II (ANG II), which is mainly responsible for vasoconstriction with consequent impact on the increment of diastolic blood pressure. They are collectively part of the renin-angiotensin system. Their components also seem to act in the brain, and ACE, ANG II and angiotensin 1 receptor have been found in the brains of Alzheimer’s disease (AD) patients.
It is hypothesized that some drugs used for the treatment of hypertension such as perindopril and captopril could be effective in attenuating some inflammatory and microglial markers in the brains of animal models of AD. For this reason, Israeli researchers investigated the effect of intranasally-administered perindopril and captopril on a mouse model of AD. Their effects on nitric oxide (NO), tumor necrosis factor- α (TNF-α) release and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 microglia, CD11b and Aβ proteins were analyzed in transgenic mice (5XFAD) for AD. The animals were randomly divided into perindopril (1 mg/kg/day), captopril (5 mg/kg/day)-treated or saline-treated groups. The control group included wild-type mice treated with perindopril or captopril. They received intranasal doses every day for 3.5 weeks or 7 months.
Reduced levels of NO and TNF-α in LPS-treated microglia were observed after the treatment with perindopril and captopril. NO production has been associated with an important production of oxidative stress which causes neuroinflammation and neurodegeneration in the brain tissues of people with AD. The inhibitory effect induced by both drugs in NO was an important finding. However, this effect does not appear to be associated with bradykinin receptor antagonists or ANG II. iNOS levels were reduced by about 50 % in LPS-stimulated cells after 24 h-treatment with perindopril or captopril. Captopril also inhibited microglial TNF-α production, and both drugs were capable of reducing CD11b expression, as well as attenuating microglia/macrophages accumulation, Aβ deposition, and amyloid burden.
Perindopril and captopril administered intranasally are effective for reducing inflammatory and microglial markers. Both drugs are important modulators for avoiding neurodegeneration and neuroinflammation, and may represent a significant strategy against Alzheimer’s disease.
Written By: Vagner Raso