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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2015-05-04T00:00:00-04:00" class="date-display-single">May 4, 2015</span></p><div class='syndicate'><h1>Structure of a Key Blood Pressure Regulator</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul class="spaced">
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<li>Scientists revealed the molecular structure of a key target for blood pressure medications.</li>
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<li>The findings may aid the development of blood pressure drugs with fewer side effects. </li>
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<picture title="Female doctor measuring blood pressure of senior woman">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2015/05-04-2015-pressure.jpg?itok=x9CkBt3A&timestamp=1430846583 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2015/05-04-2015-pressure.jpg?itok=PpHUAwUz&timestamp=1430846583 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2015/05-04-2015-pressure.jpg?itok=r00RIs_z&timestamp=1430846583 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2015/05-04-2015-pressure.jpg?itok=BYr_3ZfC&timestamp=1430846583 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2015/05-04-2015-pressure.jpg?itok=x9CkBt3A&timestamp=1430846583" alt="Female doctor measuring blood pressure of senior woman." title="Female doctor measuring blood pressure of senior woman" />
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</picture><span class="caption">Angiotensin receptor blockers are used to treat high blood pressure, but can have other effects. Understanding the receptor’s structure and how medications interact with it will help in the design of more effective drugs. </span><span class="credit">AlexRaths/iStock</span></div>
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</div><p>About 1 in 3 American adults has high blood pressure. This increases their risk of many conditions, including heart attack, heart failure, and stroke.</p>
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<p>One of the ways the human body regulates blood pressure is through a molecule called the angiotensin II type 1 receptor (AT1R). When the hormone angiotensin II binds to this receptor, it activates a pathway involving signaling molecules called G-proteins that constricts blood vessels and raises blood pressure. AT1R also activates other signaling pathways with different functions. For example, it can activate a pathway involving beta-arrestin proteins that reduces blood pressure and has other cardiovascular benefits.</p>
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<p>High blood pressure is often treated with drugs called angiotensin receptor blockers (ARBs), which include losartan, candesartan, valsartan, irbesartan, telmisartan, and eprosartan. These drugs reduce blood pressure by blocking the G-protein pathway, relaxing and widening blood vessels. But they can also block the beneficial effects of AT1R and cause negative side effects, such as dizziness and headache. Designing drugs that block only the harmful G-protein pathway would allow the beneficial pathways to continue working as blood pressure is reduced. Creating such drugs would require detailed knowledge of AT1R’s molecular structure, which has been difficult to figure out.</p>
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||
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||
<p>A team of researchers led by Dr. Vadim Cherezov at the University of Southern California used a novel X-ray crystallography technique called serial femtosecond crystallography to reveal the receptor’s structure. Extremely bright, brief pulses of an X-ray free-electron laser allowed the researchers to obtain structural information from tiny micron-sized crystals at room temperature and without radiation damage. The study, which was partially funded by NIH’s National Institute of General Medical Sciences (NIGMS) and National Heart, Lung, and Blood Institute (NHLBI), was published online in <em>Cell </em>on April 23, 2015.</p>
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||
<p>The researchers were able to determine the structure of AT1R when bound to an angiotensin receptor blocker called ZD7155. They specifically identified the components that make up the receptor’s binding pocket, where the blockers bind to cause their effects. Mutating these parts of the protein revealed which specific amino acids in the receptor were critical for binding. The researchers used this information to develop simulations of what happens in the binding pocket when other angiotensin receptor blockers bind to it.</p>
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||
<p>Of current drugs, Cherezov says, “It’s like using a 2-by-4 to kill a fly. Yes, it works, but perhaps a more refined approach could achieve the positive results without many side effects by only blocking the G-protein pathway while keeping the arrestin pathway active. To do so, you need to understand exactly how and where drug-like molecules bind to the receptor and what conformational changes they produce.”</p>
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<p>The researchers expect that their findings could lead to more effective drugs that cause fewer side effects.</p>
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<p>— by Brandon Levy</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/program-improves-blood-pressure-control" target="_top">Program Improves Blood Pressure Control</a></li><li><a href="https://newsinhealth.nih.gov/issue/Feb2012/Feature1" target="_top">Love Your Heart – Take Steps To Reduce Heart Risks</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/blood-pressure-kidney-disease-african-americans" target="_top">Blood Pressure and Kidney Disease in African-Americans</a></li><li><a href="http://www.nhlbi.nih.gov/health/health-topics/topics/hbp/" target="_top">What Is High Blood Pressure?</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/25913193">Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography.</a> Zhang H, Unal H, Gati C, Han GW, Liu W, Zatsepin NA, James D, Wang D, Nelson G, Weierstall U, Sawaya MR, Xu Q, Messerschmidt M, Williams GJ, Boutet S, Yefanov OM, White TA, Wang C, Ishchenko A, Tirupula KC, Desnoyer R, Coe J, Conrad CE, Fromme P, Stevens RC, Katritch V, Karnik SS, Cherezov V. <em>Cell</em>. 2015 Apr 21. pii: S0092-8674(15)00428-6. doi: 10.1016/j.cell.2015.04.011. [Epub ahead of print]. PMID: 25913193.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of General Medical Sciences (NIGMS) and National Heart, Lung, and Blood Institute (NHLBI); National Science Foundation; Helmholtz Gemenscheift; DFG Cluster of Excellence Center for Ultrafast Imaging; BMBF project; PIER Helmholtz Graduate School and Helmholtz Association; and Chinese 1000 Talent Program.</p>
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<div about="/block/research-matters---popular-stori" class="ds-1col entity entity-bean bean-research-matters-block view-mode-default clearfix">
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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||
|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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