Cardiovascular risks related to high dietary salt

Graphic of salt pouring on top of a person's headAccording to the American Heart Association (AHA), cardiovascular disease is the number one cause of death in the United States in both men and women. Hypertension or high blood pressure, the most prevalent form of the disease, affects at least 34 percent of US adults and an estimated 18-20 percent of adolescents. Because hypertension plays a key role in the development of life-threatening heart disease, stroke, and other serious illnesses, biomedical researchers remain focused on understanding its causes, prevention, and treatment. Although many blood pressure-lowering medications are available, few patients with hypertension have well-controlled blood pressure. One reason for this is that a large component of blood pressure control is neurally mediated, and according to Sean Stocker, Ph.D., associate professor of cellular and molecular physiology at the College of Medicine.

“The key neural pathways and mechanisms that allow our sympathetic nervous system (SNS) to tightly regulate blood pressure are still not well defined,” Stocker said. A major factor in the brain’s control of blood pressure is dietary sodium intake. Understanding how the brain responds to plasma sodium levels is likely to be particularly important, because excess dietary salt intake is expected to pose a public health epidemic of hypertension in the coming years. The mechanism by which the brain senses and reacts to plasma sodium concentration is largely unknown, and how to control the process is a major therapeutic challenge for managing hypertension.

Stocker is the recipient of the AHA’s prestigious Established Investigator Award for his research looking at the effects of salt on cardiovascular function and disease, research initially supported by CURE funds. This five-year research grant is awarded to only sixteen researchers across the United States and is based on both contributions to and future promise in cardiovascular research. Along with Penn State colleagues in the Department of Neural and Behavioral Sciences, Kirsteen Browning, Ph.D. and Alberto Travagli, Ph.D., Stocker has found that the organum vasculosum, a portion of the hypothalamus, is highly sensitive to changes in plasma sodium concentration, showing increased neural excitability with even small increases in plasma sodium. This hypothalamic region is uniquely positioned to be an interface between the peripheral circulation and the brain, because unlike other portions of the brain, it lacks a blood-brain barrier and therefore is exposed to blood circulating throughout the rest of the body.

Although we all possess these salt-sensing neurons, not all of us react to dietary sodium in the same way. “People are defined as either salt-resistant or salt-sensitive. Traditionally, salt-sensitive people are considered to be at a much higher risk for hypertension and cardiovascular disease, whereas salt-resistant people are considered protected,” Stocker said. But recent findings from Stocker’s laboratory challenge this notion.

“We have evidence to suggest that eating a diet high in salt places even salt-resistant people at risk for cardiovascular disease.” As part of a new translational research collaboration with clinical cardiovascular researchers at Penn State College of Medicine, including Kevin Monahan, Ph.D., Cardiology, and Lawrence Sinoway, M.D., director, Penn State Hershey Heart and Vascular Institute, Stocker has found that when salt-resistant animals and humans are fed a high-salt diet, they display exaggerated cardiovascular responses (blood pressure, sympathetic outflow, and heart rate) to a number of different stressors. In addition, blood pressure is much more variable through the day, and increased blood pressure variability has been correlated with adverse cardiovascular events. This occurred despite a normal blood pressure at baseline or unstressed conditions. “We can only conclude that even in salt-resistant humans and animals, a high salt diet can cause changes in how the sympathetic nervous system regulates blood pressure,” Stocker says. “The larger swings in blood pressure and heart rate during exercise in these subjects suggest a high risk of a cardiovascular event when they are given a diet high in salt.”

“With a high-salt diet, even so-called salt-resistant animals and humans, who may have normal blood pressure while they are sitting or inactive, are probably at elevated risk for heart attack or stroke. This has important implications for dietary sodium recommendations,” Stocker says.

– By Karen Dougherty

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