NIH-supported study finds novel pathway may open doors for new blood pressure treatments

June 21, 2010

Researchers have found that increasing certain proteins in the blood vessels of mice, relaxed the vessels, lowering the animal's blood pressure. The study provides new avenues for research that may lead to new treatments for hypertension.

"The paper demonstrates that cytochrome P450 plays an important role in the management of high blood pressure, a disease of enormous public health concern," said Darryl Zeldin, M.D., acting clinical director of the National Institute of Environmental Health Sciences (NIEHS) and senior author on the paper.

According to the Centers for Disease Control and Prevention, about 1 in 3 adults in the United States has high blood pressure, which increases the risk for heart disease and stroke, the first and third leading causes of death in the United States.

The study, published online in The FASEB Journal, was conducted by researchers at NIEHS who teamed with investigators at the University of North Carolina at Chapel Hill (UNC), Medical College of Wisconsin, Milwaukee, and Oregon Health and Science University, Portland.

The researchers created animal models that had a human cytochrome P450 (CYP450 or P450) in the cells that line their blood vessels. The mice with the P450 generated more substances called epoxyeicosatrienoic acids or EETs, known for their role in protecting the cardiovascular system. EETs relax and dilate the blood vessels and fight inflammation.

"We found that when the animals were exposed to substances known to increase blood pressure, the animals with the P450 had lower blood pressure and less damage to the kidneys compared to normal mice," said Craig R. Lee, Pharm.D., Ph.D., assistant professor at UNC and lead author on the paper. "We hope that these studies will advance the development of new treatments for high blood pressure."

"This is a great example of a basic finding that improves our understanding of a metabolic pathway that can be used to develop improved treatments for those suffering from a common disease like hypertension," said Linda Birnbaum, Ph.D., director of the NIEHS and the National Toxicology Program.
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For more information on hypertension, visit http://www.nhlbi.nih.gov/health/dci/Diseases/Hbp/HBP_WhatIs.html.

The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit our Web site at http://www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists (http://www.niehs.nih.gov/news/releases/newslist/index.cfm) to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. Reference: Lee CR, Imig JD, Edin ML, Foley J, DeGraff LM, Bradbury JA, et al. 2010. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. FASEB J. Epub ahead of print 2010 May 21, doi:10.1096/fj.10-160119.

NIH/National Institute of Environmental Health Sciences

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