Posted on 08/16/2011 4:29:41 PM PDT by decimon
Researchers at the Johns Hopkins University School of Medicine have found a protein normally involved in blood pressure regulation in a surprising place: tucked within the little "power plants" of cells, the mitochondria. The quantity of this protein appears to decrease with age, but treating older mice with the blood pressure medication losartan can increase protein numbers to youthful levels, decreasing both blood pressure and cellular energy usage. The researchers say these findings, published online during the week of August 15, 2011, in the Proceedings of the National Academy of Sciences, may lead to new treatments for mitochondrial–specific, age-related diseases, such as diabetes, hearing loss, frailty and Parkinson's disease.
"We've identified a functional and independently operated system that appears to influence energy regulation within the mitochondria," explains Jeremy Walston, M.D., professor of geriatric medicine at Hopkins. "This mitochondrial angiotensin system is activated by commonly utilized blood pressure medications, and influences both nitric oxide and energy production when signaled."
Previous research showed that manipulating angiotensin in the body's cells had unexpectedly affected mitochondrial energy production, so Walston and Peter Abadir , M.D., an assistant professor of geriatric medicine, decided to examine the role of angiotensin within the mitochondria. Using high-powered microscopy, they and their collaborators found evidence within the mitochondria of angiotensin as well as one of the protein receptors that bind to and detect it. They also pinpointed the angiotensin receptor's exact locations within the mitochondria of mouse kidney, liver, neuron and heart cells as well as in human white blood cells.
The team then treated mitochondria with a chemical known to activate the angiotensin receptors and measured the cell's response. This resulted in a decrease in oxygen consumption by half and a small increase in nitric oxide production—indicating less energy made by the mitochondria and lowered blood pressure, respectively. Explains Walston, "Activating angiotensin receptors within the mitochondria with these agents led to lowered blood pressure and decreased cellular energy use."
But they found even more than just an energy-regulating mechanism; after testing the angiotensin system in mitochondria of both young and old mice, they noticed a decrease by almost a third of the amount of the angiotensin receptor type 2 in the mitochondria in older mice, meaning that cells in older mice were unable to control energy use as well. The researchers then tried treating these older mice with the blood pressure lowering drug losartan daily for 20 weeks and found that the number of these receptors increased. "Treatment of the old mice with losartan resulted in a marked increase in the number of receptors that are known to positively influence blood pressure and decrease inflammation," says Walston.
Declining mitochondria are known to influence chronic diseases in older adults, explains Walston, whose next step is to translate studies from cell culture and animal based studies to human studies in hopes of developing new therapies. "Our findings will help us determine if the drugs that interact with this receptor will also lead to improvement of mitochondrial function and energy production. This, in turn, could facilitate the treatment of a number of chronic diseases of older adults."
###
This study was funded by the Johns Hopkins Older Americans Independence Center, the National Institute on Aging and the American Geriatrics Society.
Additional authors on this study from the Division of Geriatric Medicine and Gerontology at Johns Hopkins were Peter Abadir, Alka Jain, and Neal Fedarko.
Ping
"Amen" to the first part and "Hallelujah" to the second.
Maybe I’m gonna get lucky ! >PS
Whole lotta pipers here tonight.
We three are joining the geezer set?
I dunno. Howz their drum section?
I dunno. Howz their drum section?
Stretched pretty thin.
Mysterious mitochondria ping.
Thanks for the ping. This could be very important.
The good news is losartan went generic last year. The bad news is it still seems a bit pricey.
Thanks for the link.
Well, I checked. It's not yet. PNAS is fairly tardy, IMHO. This is the last paper from Walston and Abadr/Abadir(sp?) at PubMed.
FReepmail me if you want on or off the diabetes ping list.
Doc put me on 100mg of this yesterday Cazaar, but there is a cheap generic. Took me off Metropolol, hope for a good outcome.
Check around I saw it on internet yesterday for &18.00 I think at Walmart. Else you can pay $1.80 a pill.
It's called metoprolol, a beta blocker, which are prescribed routinely for the secondary prevention of myocardial infarction, i.e. a heart attack from coronary artery disease, even though taking a beta blocker is a risk factor for developing type 2 diabetes.
It's not a simple business. Depending on your history, you may want to take a low dose combination of both a low dose of a beta blocker and either an angiotensin receptor blocker(ARB) like Cozaar or an angiotensin converting enzyme(ACE) inhibitor.
Beta blockers, ACE inhibitors and ARBs are also routinely used for controlling high blood pressure. ACE inhibitors and ARBs should be preferred in type 2 diabetics with no history of myocardial infarction, IMHO.
Thanks for the info, I will add back half of the metoprolol, since BP was running a little high, will still take the Cozaar to see if BP comes down to a suitable range.
So far my HBA1C has been good, even though under the new guidelines which I think they backed off on, I was borderline. Most Doctors I have been to lately seem to ignore spot Blood Sugar and rely on HBA1C only.
I had 3 stints drilled in about a year ago, and a first heart attack 30 years ago. So I have been very fortunate health wise to be here.
About a year ago my GP found an acoustic Neuroma, so I opted for Proton Radiation therapy, but there was some disagreement between the experts whether the tumor had continued to enlarge, I have a gut feeling it is, but hoping that some of my symptoms are medication related since nearly all the BP meds slow us down.
At my age they just hope you die before it gets too debilitating, and since my Wife retired I am at the mercy of medicare and a Blue Cross PPO as secondary.
Tried very hard to beat Obamacare to the punch, but the dang neuroma detoured me a little.
Again thanks for the heads up.
bump for later reading
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.