"Under conditions of heavy, persistent mechanical load, the heart's fine-tuned calcium control system becomes unstable, causing irregular heartbeats," says Chen-Izu. "This could explain why high blood pressure can increase arrhythmias, which may lead to sudden cardiac death, heart failure, and stroke." (Credit: Jason Saul/Flickr)

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Why high blood pressure can lead to abnormal heartbeats

Scientists have found a key biological trigger that makes the heart beat stronger in response to higher blood pressure. A new study suggests there may be a way to turn that trigger off when it becomes overactive.

“The heart is a robust pump that can compensate for short-term increases in blood pressure due to changes in physical and emotional conditions—like exercise or joy,” says study senior author Ye Chen-Izu, assistant professor of pharmacology and biomedical engineering at UC Davis. “But there is a darker side to that compensating system that could lead to life-threatening heart diseases. Our work opens up new avenues for preventing that outcome.”

‘Cell-in-gel’

Chen-Izu pulled together a team of biophysicists, chemists, engineers, physiologists, and cardiologists for a study of the biological system that controls contractility of the heart under mechanical stress, such as that caused by high blood pressure. They put heart muscle cells from mice into a “cell-in-gel” system that simulates mechanical stress on cells.

The system, which was developed by Chen-Izu and Kit Lam, chair of the biochemistry and molecular medicine department, is transparent. This allows them to see changes in living cells at the molecular level using powerful microscopes.

A series of experiments showed that as mechanical stress increases, the release of calcium increases, which strengthens heart contractions so it can pump harder against higher blood pressure. They identified a protein known as nitric oxide synthase, or NOS, as the molecule that initially senses mechanical stress and creates nitric oxide, which activates ryanodine receptors that increase the calcium release.

The researchers also discovered that an isoform of NOS—neuronal nitric oxide synthase, or nNOS—was responsible for spontaneous calcium sparks that occurred when cells were supposed to rest, likely due to the buildup of nitric oxide from ongoing mechanical stress.

Irregular heartbeats

“Under conditions of heavy, persistent mechanical load, the heart’s fine-tuned calcium control system becomes unstable, causing irregular heartbeats,” says Chen-Izu, whose research focuses on the biomechanics and bioelectricity of heart disease. “This could explain why high blood pressure can increase arrhythmias, which may lead to sudden cardiac death, heart failure, and stroke.”

Additional experiments showed that a known nNOS inhibitor reduced calcium sparks while cells were responding to mechanical load, suggesting that the molecule is a key factor in instigating abnormal heartbeats.

Additional researchers from UC Davis were joined by others from the University of Michigan, the University of Debrecen in Hungary, and the University of Arizona. The results of the study are published in the journal Science Signaling.

The National Institutes of Health, a US Veteran’s Affairs Merit Review Grant, and funding from UC Davis supported the research.

Source: UC Davis

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