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Genes and drugs team up to lower blood pressure

09-12-2007 · EurekAlert!

Patients with high blood pressure respond very differently to anti-hypertensive medication, making treatment selection tricky for physicians. But new research published in the online open access journal, BMC Medical Genetics, pinpoints a number of gene-drug interactions that could allow medication to be tailored to individual patients based on their genetics.

Keywords: genes, drugs, team, lower, blood, pressure, gene, drug

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Advance in understanding of blood pressure gene could lead to new treatments
02-04-2007 · EurekAlert!
Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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A relative of anti-aging gene Klotho also influences metabolic activity, obesity
04-23-2007 · UT Southwestern Medical Center
A relative of the anti-aging gene Klotho helps activate a hormone that can lower blood glucose levels in fat cells of mice, making it a novel target for developing drugs to treat human obesity and diabetes, UT Southwestern Medical Center researchers have found.
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Common blood pressure drug treats muscular dystrophy in mice
01-21-2007 · EurekAlert!
Researchers at Johns Hopkins have shown that a drug commonly used to lower blood pressure reverses muscle wasting in genetically engineered mice with Marfan syndrome and also prevents muscle degeneration in mice with Duchenne muscular dystrophy. The results are reported online this week at Nature Medicine.
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Researchers discover surprising drug that blocks malaria
01-15-2007 · EurekAlert!
Northwestern University researchers have uncovered how malaria parasites break into red blood cells and how to block the invading parasites with a commonly prescribed high-blood pressure medication. This opens the door for important new drugs to which the parasites are much less likely to become resistant. Malaria is surging worldwide because of drug resistance and the lack of an effective vaccine. Jamaica, which had eradicated the disease for 50 years, recently reported an outbreak.
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Gene expression profiling of dengue virus infection in cell lines and patients
11-06-2007 · EurekAlert!
Researchers at the Novartis Institute for Tropical Diseases and the Genome Institute of Singapore have identified new host genes associated with dengue virus infection, which may open new avenues to developing a drug to treat the disease. The results suggest that drugs that target the host pathways may prove effective against dengue.
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JCI table of contents: Aug. 16, 2007
08-16-2007 · EurekAlert!
This release contains summaries, links to PDFs and contact information for the following newsworthy papers to be published online, Aug. 16, 2007, in the JCI, including: "Can cancer drugs combine forces?"; "Specific antagonism lowers blood pressure"; "Eyeing up a role for S1P2R in abnormal blood vessel formation"; "A winning combination for the treatment of cancer"; "How tumors prevent immune cell entry"; and "1, 2, 3: third gene responsible for genetic disorder identified."
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Prescribing information for kidney disease far too vague
12-06-2006 · EurekAlert!
Prescribing information for healthcare professionals treating patients with kidney disease is too vague, concludes the latest issue of Drug and Therapeutics Bulletin (DTB). Many of the 4-5 percent of the UK population with serious chronic kidney disease are elderly people, who are often taking several different drugs. Other risk factors for the disease include diabetes and high blood pressure.
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Health providers could save billions without compromising healthcare says drug study
01-17-2007 · EurekAlert!
Switching patients to more cost-effective drugs for cholesterol and blood pressure problems could reduce health budgets by billions without compromising clinical care, according to a study in the January issue of IJCP, the International Journal of Clinical Practice. No adverse events were reported after patients were switched -- the new cholesterol drugs delivered the same results as the previous drug and the new blood pressure drugs delivered improved performance.
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UGA study suggests that lowering blood pressure following stroke may reduce damage
04-17-2007 · EurekAlert!
A new University of Georgia study suggests that commonly prescribed drugs used to lower blood pressure may help reduce brain damage when given within 24 hours of a stroke. The finding, based on a study using rats and published in the April issue of the Journal of Hypertension, may ultimately revolutionize emergency stroke care by putting blood pressure-lowering medications alongside clot-busting drugs and blood thinners as front-line medications.
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Only half of hypertensive California adults take blood pressure-lowering drugs
09-28-2007 · EurekAlert!
About half of California adults diagnosed with high blood pressure, or hypertension, do not take medication to lower it, researchers reported today at the American Heart Association's 61st Annual Fall Conference of the Council for High Blood Pressure Research.
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