High blood pressure, or hypertension, is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. And secret to treating patients with ailments ranging from chest discomfort to stroke is comprehending the intricacies of the way the cells round arteries and other blood vessels operate to control blood pressure. While the importance of metals such as calcium and potassium in this process are known, a new discovery of an essential and underappreciated role of some other alloy – zinc – provides a potential new pathway for therapies to treat hypertension.
The study results were published in Nature Communications.
All the body’s functions depend on arteries channeling oxygen-rich blood – energy – to where it is needed, and smooth muscle cells inside these vessels direct how slow or fast the blood gets to every destination. As smooth muscles contract, they narrow the artery and increase blood pressure, as well as the muscle relaxes, the artery expands and blood pressure falls. If the blood pressure is too low the blood circulation won’t be enough to sustain a person’s body with oxygen and nutrients. If the blood pressure is too high, the blood vessels risk being damaged or even ruptured.
“Fundamental discoveries going back more than 60 years have established that the levels of the calcium and potassium in the muscle surrounding blood vessels control how they expand and contract,” say lead author Ashenafi Betrie, Ph.D., and senior authors Scott Ayton, Ph.D., and Christine Wright, Ph.D., of the Florey Institute of Neuroscience and Mental Health and The University of Melbourne in Australia.
Specifically, the researchers explain, potassium modulates calcium from the muscle, and calcium is known to be responsible for causing the narrowing of the arteries and veins that elevate blood pressure and restrict blood flow. Other cells that surround the blood vessel, including endothelial cells and sensory nerves, also modulate the calcium and potassium inside the muscle of this artery, and are themselves regulated by the levels of the metals contained inside them.
“Our discovery that zinc is also important was serendipitous because we’d been researching the brain, not blood pressure,” says Betrie. “We were investigating the impact of zinc based drugs on brain function in Alzheimer’s disease when we noticed a pronounced and unexpected decrease in blood pressure in mouse models treated with the drugs.”
In cooperation with researchers at the University of Vermont’s Larner College of Medicine in the United States and TEDA International Cardiovascular Hospital in China, the researchers learned that coordinated activity by zinc within sensory nerves, endothelial cells as well as the muscle of arteries triggers lower calcium levels in the muscle of the blood vessel. This produces the vessel relax, decreasing blood pressure and increasing blood circulation. The scientists found that blood vessels in the brain and the center were more sensitive to zinc than blood vessels in different regions of the body – an observation that warrants further study.
“Essentially, zinc has the opposite effect to calcium on blood flow and pressure,” says Ayton. “Zinc is an important metal ion in biology and, given that calcium and potassium are famous for controlling blood flow and pressure, it’s surprising that the role of zinc hasn’t previously been appreciated.”
Another surprising fact is that genes that control zinc levels inside cells have been known to be related to cardiovascular diseases including hypertension, and hypertension is additionally a known complication of zinc deficiency. This new study provides explanations for why these previously known associations.
“While there are a range of existing drugs that are available to lower blood pressure, many people develop resistance to them,” says Wright, who added that a number of cardiovascular diseases, including pulmonary hypertension, are poorly treated by currently available therapies. “New zinc based blood pressure drugs would be a huge outcome for an accidental discovery, reminding us that in research, it isn’t just about looking for something specific, but also about just looking.”
Related Journal Article: https://www.nature.com/articles/s41467-021-23198-6