Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Studies Suggest New Key to “Switching Off” Hypertension

A team of University of California, San Diego researchers has designed new compounds that mimic those naturally used by the body to regulate blood pressure. The most promising of them may literally be the key to controlling hypertension, switching off the signaling pathways that lead to the deadly condition.

Published online this month in Bioorganic & Medicinal Chemistry, the scientists studied the properties of the peptide called catestatin that binds nicotinic acetylcholine receptors found in the nervous system, and developed a pharmacophore model of its active centers.

Catestatin-mimic pharmacophore model. Pharmacophore centers correspond to hydrophobic residues Leu5, Phe7, and Phe14; and positively charged residues Arg8, Arg10, and Arg15. Green circles represent hydrophobes and aromatic/hydrophobic features, while dark-blue circles represent NCN+ groups/cations/H-bond donors. Ribbon diagram and three-dimensional residue structures belong to superimposed catestatin. Image courtesy of Valentina Kouznetsova, UC San Diego.

They next screened a library of compounds for molecules that might match this 3D “fingerprint”. The scientists then took their in-silico findings and applied them to lab experiments, uncovering compounds that successfully lowered hypertension.

“This approach demonstrates the effectiveness of rational design of novel drug candidates,” said lead author Igor F. Tsigelny, a research scientist with the university’s San Diego Supercomputer Center (SDSC), as well as the UC San Diego Moores Cancer Center and the Department of Neurosciences.

“Our results suggest that analogs can be designed to match the action of catestatin, which the body uses to regulate blood pressure,” said Daniel T. O’Connor, a professor at the UC San Diego School of Medicine and senior author of the study. “Those designer analogs could ultimately be used for treatment of hypertension or autonomic dysfunction.”

The research may lead to a new class of treatments for hypertension, a disease which affects about 76 million people, or about one in three adults, in the United States, according to the American Heart Association. Untreated, it damages the blood vessels and is a leading risk factor for kidney failure, heart attack, and stroke.

Despite being a common and lethal cardiovascular risk factor, hypertension remains only partially controlled by current antihypertensive medications, most of which have serious side effects. Specifically, the SDSC/UC San Diego researchers targeted the hormone catestatin for therapeutic potential. Catestatin acts as the gatekeeper for the secretion of catecholamines – hormones that are released into the blood during times of physical or emotional stress. A drug that mimics the action of catestatin would thus allow people to control the hormones that regulate blood pressure.

Based on earlier studies of the structure of catestatin, O’Connor, Tsigelny, and their colleagues figured out which residues of catestatin are responsible for binding to the nicotinic receptor – similar to mapping how the ridges on a key fit into a lock. They created a three-dimensional model of the most important binding centers – the pharmacophore model. Then they screened about 250,000 3D compound structures in the Open NCI Database to select ones that fit this fingerprint of active centers. They discovered seven compounds that met the requirements, and tested those compounds in live cells to gauge their effects on catecholamines. Based on their findings, they tried one compound (TKO-10-18) on hypertensive mice, and showed that this compound produced the same anti-hypertensive effect as catestatin.

“Analysis of the catestatin molecule yielded a family of small organic compounds with preserved potency and pathway specificity,” said Valentina Kouznetsova, PhD, an associate project scientist at SDSC and the UC San Diego Moores Cancer Center. “Further refinement of our model should lead to the synthesis and development of a novel class of antihypertensive agents.”

Authors include SDSC’s Tsigelny, O’Connor, and Kouznetsova, as well as Nilima Biswas and Sushil K. Mahata, of UC San Diego’s Departments of Medicine and Pharmacology.

Media Contact

Cassie Ferguson,
Secondary media contact:
Jan Zverina, 858-534-5111,

Cassie Ferguson | EurekAlert!
Further information:

Further reports about: Cancer blood pressure blood vessel hypertension risk factor

More articles from Life Sciences:

nachricht Make way for the mini flying machines
21.03.2018 | American Chemical Society

nachricht New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

TRAPPIST-1 planets provide clues to the nature of habitable worlds

21.03.2018 | Physics and Astronomy

The search for dark matter widens

21.03.2018 | Materials Sciences

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>