• Calcium and potassium are involved in the regulation of blood pressure, but one new study suggests that zinc may also have a part to play.
• The researchers made this discovery accidentally while they were investigating zinc’s role in rat brain function.
• If additional research validates the study’s conclusion, the findings could eventually lead to new drugs for controlling hypertension, or high blood pressure.

Doctors use a variety of strategies to help people manage hypertension. When exercise and dietary measures, such as increasing potassium intake and reducing salt intake, are not enough to keep blood pressure within acceptable limits, many drugs are available.

Each of them attempts to either reduce cardiac output or reduce peripheral resistance in the body’s arterial system. One mechanism for reducing resistance to blood flow is to relax the muscles that surround the arteries and arterioles, allowing blood to flow more freely.

“Fundamental discoveries going back more than 60 years have established that the levels of calcium and potassium in the muscle surrounding blood vessels control how they expand and contract,” say the authors of a recent study. However, these scientists unexpectedly found that a metal, zinc, may also play a role in maintaining vascular tone.

Senior study author Dr. Scott Ayton, Ph.D., says:

“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.”

Dr. Ayton adds, “Essentially, zinc has the opposite effect to calcium on blood flow and pressure.”

The study’s lead author is Dr. Ashenafi Betrie, Ph.D., and the co-senior author is Dr. Christine Wright, Ph.D. They and Dr. Ayton are all affiliated with the Florey Institute of Neuroscience and Mental Health in Parkville, Australia, and the University of Melbourne, also in Australia.

The study appears in the journal Nature Communications.

A surprising discovery

“Our discovery that zinc is also important was serendipitous because we’d been researching the brain, not blood pressure,” says Dr. Betrie.

As Dr. Betrie recalls, “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 rat models treated with the drugs.”

The researchers’ discovery may explain a couple of things that experts already know about zinc. First, zinc deficiency has been associated with hypertension in animal models. Second, the gene responsible for maintaining zinc levels within cells is also linked to hypertension and other cardiovascular diseases.

However, in human studies, there is no evidence of a link between dietary intake of zinc and hypertension. The amount of zinc in the bloodstream does not correlate with the amounts in the cell. This study found that it is the amount of zinc inside cells that is important.

How zinc may affect blood pressure

High blood pressure occurs when the smooth muscle cells in artery and arteriole walls contract, narrowing these vessels through which blood needs to flow.

The blood pushes out the walls of these narrowed passages as it forces its way through, creating a potentially destructive increase of outward pressure on them. This can result in damaged or even ruptured blood vessels.

Calcium in the muscles causes this tightening. The calcium is regulated by potassium in the muscle tissue. The quantity of both metals is influenced by surrounding cells, such as endothelial cells and sensory nerves, which are themselves regulated by the potassium and calcium they contain.

The researchers found that zinc affects the muscles, endothelial cells, and sensory nerves together, reducing the amount of calcium in the muscles and causing them to relax. This, in turn, results in increased blood flow and lower blood pressure.

Dr. Winston Morgan, from the University of East London in the United Kingdom, told Medical News Today that although other studies have suggested a possible role for zinc in hypertension, this one specifically “explores what happens when intracellular zinc is regulated upward or downward using ionophores and chelators.”

Ionophores are chemical vehicles that transport ions, such as zinc, across a cell membrane, while chelators bind them. The researchers suggest that increasing intracellular zinc using an ionophore may have led to lower blood pressure in the rats they were studying.

The scientists also conducted laboratory experiments on selected blood vessels from both rats and humans and found that when they reduced intracellular zinc using a chelator, these vessels contracted.

Dr. Morgan added, “Exciting as the results are, they are only suggestive of the proposed mechanism.” They also leave a number of important questions unanswered. The study authors state that more research needs to investigate how zinc affects different cell types and pathologies.

The researchers also note that the blood vessels of the heart and brain proved to have a greater sensitivity to zinc than blood vessels elsewhere in the body.

A new tool in hypertension management

The study’s discovery may suggest a promising avenue for further investigation. However, Donna Arnett, Ph.D. — a professor of epidemiology at the University of Kentucky College of Public Health in Lexington — cautioned MNT that “based on the first study done in mesenteric arteries in rats, there should not be a recommendation for humans to start zinc given there are no studies in humans.”

Dr. Morgan also noted, “In this study, when zinc was added externally, it had no effect on vascular tone. It was only effective when intracellular levels were artificially elevated using the ionophores, which are rarely a therapeutic option.”

If subsequent research does eventually validate zinc’s role in blood pressure management, a new hypertension treatment option would be welcome.

As Dr. Wright says, “While there are a range of existing drugs that are available to lower blood pressure, many people develop resistance to them.” It is also the case that certain existing drugs may produce problematic side effects for some people.

Dr. Wright concludes:

“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.”

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