Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Action of nitroglycerin for chest pain may place some patients at risk

16.08.2005


Definitive evidence to explain how the drug nitroglycerin relieves chest pain has resulted from a new study by Howard Hughes Medical Institute investigators at Duke University Medical Center. Nitroglycerin relaxes blood vessels to boost blood flow, yet the mechanism by which the drug works has remained a matter of scientific controversy.



The findings bolster earlier indications that the drug may be ineffective for certain patients, and may place others at risk, the researchers said. The results also suggest that certain other drugs should be avoided by heart patient’s taking the blood vessel dilator, as those drugs’ activity might counteract nitroglycerin’s effects. Such drugs include sulfonylureas used by diabetics, chloral hydrates used for sleep disorders and acetaminophen (e.g. Tylenol). Alcohol may also block the effect of nitroglycerin, said the researchers.

The researchers found through studies in mice that the cellular powerhouses -- known as mitochondria -- break down nitroglycerin to release nitric oxide, thereby opening blood vessels and lowering blood pressure. Nitric oxide normally present in the bloodstream plays a critical role in controlling blood vessel relaxation.


Nitroglycerin loses its effects on blood flow in animals lacking a particular mitochondrial enzyme called aldehyde dehydrogenase (mtALDH), the Duke team reported in the August 23, 2005, Proceedings of the National Academy of Sciences (published early online the week of August 15).

"Doctors have prescribed nitroglycerin for the relief of chest pain for some 150 years, yet the mechanism by which the drug works has remained a matter of debate," said study author Jonathan Stamler, M.D., at Duke. "The findings confirm that mtALDH is critical for nitroglycerin action."

"The results should bring closure to long-standing scientific controversy, and will likely change the way physicians deliver nitroglycerin therapy to patients," he added. "These findings should certainly motivate a reassessment of this class of drugs."

First discovered in 1847 and brought to public prominence by the famed Alfred Nobel, who manufactured it first as an explosive, nitroglycerin is a common treatment for chest pain and heart failure. While the drug can effectively relieve chest pain, it tends to lose it effectiveness over time, Stamler said. More recent evidence has raised additional concerns about the drug’s potential to cause long-term injury to the heart, and perhaps even death.

As a result of the drug’s long history of use, its benefits for patient outcomes have never been demonstrated through the rigorous clinical trials that are now standard in cardiovascular care, Stamler explained.

In normal mice, treatment with nitroglycerin led to a drop in blood pressure, which increased with drug dose, the researchers showed.

Mutant mice lacking mtALDH lose the ability to process nitroglycerin, the team reported. As a result, the drug failed to lower blood pressure in the mutant mice at doses comparable to those prescribed to patients.

"The current study finds that mtALDH is both necessary and sufficient for generating vasodilation from clinically relevant levels of nitroglycerin," Stamler said.

Animals unable to process nitroglycerin continued to respond to alternative nitrate drugs that dilate blood vessels, suggesting that those drugs work through an independent mechanism.

"We thought that all of these drugs worked in the same way through the release of nitric oxide," Stamler said. "The current findings require us to revisit the implications of the use of these drugs."

Chronic use of the drug could lead to mitochondrial damage, which may ultimately increase patients’ cardiovascular risk, Stamler said. Therefore, the drug should be prescribed judiciously, he added.

Sustained use of the drug might place some patients at particular risk, Stamler said. For example, physicians should use caution in treating patients, such as those with diabetes, who often already suffer mitochondrial damage.

The drug might also be less effective for patients with particular variants of the ALDH gene. Notably, many Asian people carry a mutant version of the gene characterized by reduced ALDH activity. The lower activity enzyme would leave such patients less responsive to nitroglycerin therapy, Stamler said.

Furthermore, he added, patients taking nitroglycerin should perhaps avoid taking other classes of drugs that also inhibit activity of the mitochondrial enzyme. They include sulfonylureas, chloral hydrates and acetaminophen. Alcohol may also block the effect of nitroglycerin, Stamler said.

"Heart patients who take nitrate drugs such as nitroglycerin might do better if they did not take other drugs with effects on this enzyme," Stamler said. "Alternatively, patients taking those drugs should not be prescribed nitroglycerin. Further clinical study will be required in order to work such issues out."

Kendall Morgan | EurekAlert!
Further information:
http://www.duke.edu

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>