Angiotensin II AT(1) receptor blockers ameliorate inflammatory stress: a beneficial effect for the t

[Remy]

Abstract

Excessive allostatic load as a consequence of deregulated brain inflammation participates in the development and progression of multiple brain diseases, including but not limited to mood and neurodegenerative disorders.

Inhibition of the peripheral and brain Renin-Angiotensin System by systemic administration of Angiotensin II AT(1) receptor blockers (ARBs) ameliorates inflammatory stress associated with hypertension, cold-restraint, and bacterial endotoxin administration.

The mechanisms involved include: (a) decreased inflammatory factor production in peripheral organs and their release to the circulation; (b) reduced progression of peripherally induced inflammatory cascades in the cerebral vasculature and brain parenchyma; and (c) direct anti-inflammatory effects in cerebrovascular endothelial cells, microglia, and neurons.

In addition, ARBs reduce bacterial endotoxin-induced anxiety and depression. Further pre-clinical experiments reveal that ARBs reduce brain inflammation, protect cognition in rodent models of Alzheimer's disease, and diminish brain inflammation associated with genetic hypertension, ischemia, and stroke.

The anti-inflammatory effects of ARBs have also been reported in circulating human monocytes. Clinical studies demonstrate that ARBs improve mood, significantly reduce cognitive decline after stroke, and ameliorate the progression of Alzheimer's disease. ARBs are well-tolerated and extensively used to treat cardiovascular and metabolic disorders such as hypertension and diabetes, where inflammation is an integral pathogenic mechanism.

We propose that including ARBs in a novel integrated approach for the treatment of brain disorders such as depression and Alzheimer's disease may be of immediate translational relevance.

 

[Remy]

I am not sure why more people aren't trialing Losartan?

It's long been used in the Shoemaker protocol at a low dose (up to 25 mg twice a day) to reduce TGF-b1 and has also been an integral part of the Marshall Protocol. At these low doses, it doesn't seem to have much effect on lowering the blood pressure as it does at high doses.

It also seems to have anti-inflammatory effects on microglial cells (Younger research) and may help reduce inflammatory stress associated with endotoxin release (https://www.healthrising.org/blog/2...ain-mood-and-me-cfs-fm-part-ii-emerging-stor/)

It may also inhibit myostatin, which could explain a lot in terms of muscle wasting.

 

[weyland]

I am not sure why more people aren't trialing Losartan?

I've been thinking about it, both to lower my orthostatic hypertension as well as antagonize TGF beta.

 

[rebar]

As I have high blood pressure it looks intriguing.

 

[Not dead yet!]

"We propose that including ARBs in a novel integrated approach for the treatment of brain disorders such as depression and Alzheimer's disease may be of immediate translational relevance."

Heh, if only it were that easy...

I've recently fully stopped using a beta blocker because the headache protection is less important than the added fatigue. I wonder if an ARB can also be used in migraine prevention? If so, then why bother with beta blockers anymore?

Most anti hypertensives cause fatigue though. It took me a while to get just how badly nadolol was tiring me out. Since I'm tired anyway, it's hard to tell. And it has a very very long after-effect, nearly a week long. I had to catch on that whenever I stopped, a week later I had a headache that wasn't a migraine, it was just pounding in general. Taking decreasing doses weekly was the trick that finally worked. Then two weeks later I felt less brain fogged and more able to care for myself.

I'm not looking forward to any more anti-hypertensives, but maybe in small doses it might be ok. Trouble is, so few doctors are willing to give you something based on research alone. Some clinical guideline has to include it in the recommended treatments before many doctors will touch it.

 

[Remy]

Some clinical guideline has to include it in the recommended treatments before many doctors will touch it.

Tis sadly true. Thankfully I have a more open minded doctor...