For your stroke edification.
16 posts on Viagra here.
Impotence medicine associated with reduced long-term risk of death after heart attack March 2017
Drugs used for impotence could treat vascular dementia? December 2014
This made it sound helpful, even though it was just in rats and during the first week: viagra and stroke rehab March 2011
Sildenafil Enhances Neurogenesis and Oligodendrogenesis in Ischemic Brain of Middle-Aged Mouse November 2012
Viagra may one day help treat heart disease. Here’s why
Liz Meszaros, MDLinx | March 08, 2019
Originally developed in 1989 by researchers
at Pfizer to treat hypertension and angina pectoris, sildenafil—more
commonly known as Viagra—may put the brakes on the actions of mTOR, a
protein that plays a major role in many diseases, including heart
failure, cancer, diabetes, and autoimmune disorders, according to
researchers.
Sildenafil could become an effective
treatment for cardiac diseases in which mTORC1 is overly active,
returning almost full circle to what it was originally intended for—the
heart.
During early clinical trials of sildenafil,
however, it became evident that this drug was more effective at inducing
erections than at treating angina. Thus, it became “the little blue
pill” that changed everything for those battling erectile dysfunction.
Sildenafil—a phosphodiesterase type 5 (PDE-5) inhibitor—is currently approved for the treatment of erectile dysfunction and pulmonary arterial hypertension. By selectively inhibiting PDE-5, sildenafil improves relaxation in smooth muscle tissue. However, it is sildenafil’s activity in blocking mTORC1—a complex formed by mTOR and other proteins—that is currently causing a fuss.
In a recent study published in Nature, researchers discovered that turning on protein kinase G, the target of sildenafil, can block—rather than completely shut down—mTORC1, a protein complex that controls protein synthesis and plays a critical role in immune cell activation and memory.
Excessive amounts of mTORC1 have been shown to have damaging effects on the heart. But completely blocking mTORC1 can also cause damage.
“The problem with the few drugs that we have to manipulate mTORC1 is that they are essentially turning it off, which also shuts down its normal function in the cells,” said senior author David Kass, MD, the Abraham and Virginia Weiss Professor of Cardiology, and professor, Departments of Medicine, Pharmacology and Molecular Sciences, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD. “That means if you use it to, say, treat a tumor, you suppress the immune system as well, and might cause diabetes, or kidney and other organ damage by blocking mTORC1 in the other cells.”
Dr. Kass and colleagues detailed their findings in a murine model of a molecular “switch” that may fine-tune mTORC1 activity instead of just turning it on or off. Specifically, they found that protein kinase G can alter tuberin—a cellular “antenna”—by adding phosphates to it. Thus, the tuberin, in essence, becomes a braking mechanism for mTORC1.
They concluded that keeping the tuberin “turned down” triggered superactivity in mTORC1, and keeping tuberin “turned on” increased the braking action, keeping mTORC1 inactive in spite of stimulating hormones.
“Instead of turning mTORC1 off, we had something that looked more like a car brake, that was effective only if the car (mTORC1) was on and active,” said lead author Mark J. Ranek, PhD, Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD. “The benefit is that the new way to control mTORC1 by altering tuberin didn’t prevent its normal roles, but could keep mTORC1 in check from being turned on to too high of a level,” he added.
With these recent study results, these researchers have introduced the possibility that sildenafil could become an effective treatment for cardiac diseases in which mTORC1 is overly active, returning almost full circle to what it was originally intended for—the heart.
“This is an important finding because it reveals a novel strategy that could be employed in future potential therapeutic efforts to protect the heart from damaging stress such as high blood pressure,” concluded Bishow Adhikari, PhD, a program officer for the study, and scientist, National Heart, Lung, and Blood Institute, part of the National Institutes of Health, Bethesda, MD.
This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, American Heart Association Post-Doctoral Fellowships, Deutsche Forschungsgemeinschaft OE 688/1-1, Fondation Leducq TransAtlantic Network of Excellence, Abraham and Virginia Weiss Professorship, Erika J. Glazer Endowed Chair in Women’s Heart Health, Barbra Streisand Women’s Heart Center, and the Bloomberg-Kimmel Institute for Cancer Immunotherapy.
Sildenafil could become an effective
treatment for cardiac diseases in which mTORC1 is overly active,
returning almost full circle to what it was originally intended for—the
heart. Sildenafil—a phosphodiesterase type 5 (PDE-5) inhibitor—is currently approved for the treatment of erectile dysfunction and pulmonary arterial hypertension. By selectively inhibiting PDE-5, sildenafil improves relaxation in smooth muscle tissue. However, it is sildenafil’s activity in blocking mTORC1—a complex formed by mTOR and other proteins—that is currently causing a fuss.
In a recent study published in Nature, researchers discovered that turning on protein kinase G, the target of sildenafil, can block—rather than completely shut down—mTORC1, a protein complex that controls protein synthesis and plays a critical role in immune cell activation and memory.
Excessive amounts of mTORC1 have been shown to have damaging effects on the heart. But completely blocking mTORC1 can also cause damage.
“The problem with the few drugs that we have to manipulate mTORC1 is that they are essentially turning it off, which also shuts down its normal function in the cells,” said senior author David Kass, MD, the Abraham and Virginia Weiss Professor of Cardiology, and professor, Departments of Medicine, Pharmacology and Molecular Sciences, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD. “That means if you use it to, say, treat a tumor, you suppress the immune system as well, and might cause diabetes, or kidney and other organ damage by blocking mTORC1 in the other cells.”
Dr. Kass and colleagues detailed their findings in a murine model of a molecular “switch” that may fine-tune mTORC1 activity instead of just turning it on or off. Specifically, they found that protein kinase G can alter tuberin—a cellular “antenna”—by adding phosphates to it. Thus, the tuberin, in essence, becomes a braking mechanism for mTORC1.
They concluded that keeping the tuberin “turned down” triggered superactivity in mTORC1, and keeping tuberin “turned on” increased the braking action, keeping mTORC1 inactive in spite of stimulating hormones.
“Instead of turning mTORC1 off, we had something that looked more like a car brake, that was effective only if the car (mTORC1) was on and active,” said lead author Mark J. Ranek, PhD, Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD. “The benefit is that the new way to control mTORC1 by altering tuberin didn’t prevent its normal roles, but could keep mTORC1 in check from being turned on to too high of a level,” he added.
With these recent study results, these researchers have introduced the possibility that sildenafil could become an effective treatment for cardiac diseases in which mTORC1 is overly active, returning almost full circle to what it was originally intended for—the heart.
“This is an important finding because it reveals a novel strategy that could be employed in future potential therapeutic efforts to protect the heart from damaging stress such as high blood pressure,” concluded Bishow Adhikari, PhD, a program officer for the study, and scientist, National Heart, Lung, and Blood Institute, part of the National Institutes of Health, Bethesda, MD.
This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, American Heart Association Post-Doctoral Fellowships, Deutsche Forschungsgemeinschaft OE 688/1-1, Fondation Leducq TransAtlantic Network of Excellence, Abraham and Virginia Weiss Professorship, Erika J. Glazer Endowed Chair in Women’s Heart Health, Barbra Streisand Women’s Heart Center, and the Bloomberg-Kimmel Institute for Cancer Immunotherapy.
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