Why Is My Blood Pressure Sensitive to Salt? This Gene May Explain Why

Researchers at the School of Medicine and George Washington University School of Medicine have discovered how a gene variant found in 48 percent of the population can limit the body’s ability to eliminate excess salt after high-salt meals.

Having this gene variant increases the odds of having blood pressure that is sensitive to salt, the researchers determined previously. This follow-up discovery explains exactly how the variant prevents the body from eliminating excess salt.

Salt sensitivity of blood pressure is difficult for doctors to diagnose and even more difficult to treat because 14 percent of the population can have normal blood pressure and still be salt sensitive. Knowing precisely where the salt-elimination defect is located and how it works could eventually lead to personalized treatments for the condition.

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High Blood Pressure, Strokes and Heart Attacks

In this era of personalized medicine, physicians are recommending individualizing diet and exercise routines because everyone reacts differently to these lifestyle choices. Previously, the UVA researchers demonstrated that each individual is genetically programmed with a “personal index of salt sensitivity,” suggesting sodium chloride dietary guidelines should also be personalized. The approximate 30 percent of the population that is sensitive to salt will have a higher incidence of strokes, heart attacks, kidney failure and blindness because of the inability to eliminate sufficient sodium.

In their new findings explaining the genetic causes of salt sensitivity, the researchers determined that the genes code for a protein in the kidney that helps balance

Salt-sensitive hypertension symptoms — **Robin Felder**

sodium elimination with sodium retention. “It’s important for the body to get rid of excess sodium because having too much sodium in the body causes the body to retain water, which can raise blood pressure and significantly shorten one’s lifespan,” explained Robin A. Felder, PhD, of UVA’s Department of Pathology, the senior author of a new paper that details the discovery, published in the online journal PLOS ONE.

The research reveals that a gene defect causes a sodium transporter called NBCe2 to overwork. This brings too much sodium filtered in the kidney back into the body, especially after a high-salt meal. That means that consuming too much salt could be especially dangerous for people who carry this defective gene. “Additional studies will be necessary to examine additional sodium transporters in both animal models as well as human volunteers,” said GWU’s Pedro A. Jose, MD, a co-investigator in Felder’s salt-related research program.

The Effects of Salt

Felder’s research was based on a study population tested previously at UVA by Robert M. Carey, MD, who evaluated how the kidney metabolizes salt in a population of 183 adult volunteers who agreed to follow a special diet of high salt for one week and very low salt for another.

“We spent over five years discovering and furthering our understanding of this key pathway associated with salt sensitivity since the presence of NBCe 2, and its effect on salt excretion has never been demonstrated in the human kidney,” said Carey, of UVA’s Department of Medicine.

A recent grant from the National Institutes of Health’s National Heart, Lung and Blood Institute is allowing Felder and his colleagues to continue their studies, and they are now seeking volunteers for their ongoing salt consumption clinical trials. To learn more about these studies, please visit www.saltstudy.com.

— Update: 02-02-2023 — cohaitungchi.com found an additional article Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction from the website www.ncbi.nlm.nih.gov for the keyword salt-sensitive hypertension symptoms.

Introduction

Hypertension is a complex trait determined by both genetic and environmental factors and is a major public health problem due to its high prevalence and concomitant increase in the risk for cardiovascular disease.

Among environmental factors, dietary salt intake is the most common and important risk factor for hypertension. Salt is an essential electrolyte to the living of human beings and is used universally in cooking, seasoning, and preserving manufactured foodstuffs around the world. For several million years, human ancestors ate a diet that contained less than 1 g of salt per day. In Hunter-gathering periods, nomads hunted and ate the meat within a few hours of the kill. They do not eat salt with their food. In the mean times, population growth led to the introduction of agriculture and during the first few thousand years after the advent of agriculture, the intake of meat declined and the intake of vegetable food increased up to 90%. In this period, salt consumption in humans rose steeply. With the recent large increase of dietary salt intake in most developed countries in the world, the prevalence of hypertension increases tremendously which is about 30% of the world population1).

Evidence from clinical observations2,3), animal studies4,5,6), clinical trials7,8,9,10,11,12) shows a causal relation between dietary salt intake and hypertension. Many epidemiologic studies have also demonstrated that a high salt intake is associated with an increased risk of cardiovascular disease13,14,15,16). There is substantial evidence suggesting that blood pressure (BP) responses to dietary salt intake vary considerably among individuals which is a phenomenon described as salt sensitivity of blood pressure17,18,19).

Although salt sensitivity is a well established phenomena in experimental and human hypertension, the pathophysiologic mechanisms remain unclear. It has been suggested that abnormalities in the renin angiotensin aldosterone system20,21), the sympathetic nervous system22), renal transmembrane sodium transport23), the kallikrein-kinin system, the nitric oxide (NO) system, eicosanoids, and the vascular endothelium24,25) are all involved in the pathogenesis of salt sensitive hypertension. In the evolutionary aspects, human kidneys are well-equipped with a salt retaining function and have less efficient salt excretory functions when challenged with large amounts of salt loads. If salt intake exceeds the kidney’s ability to excrete salt, then it is accumulated in the body 26). One of the main organ systems vulnerable to the adverse effects of excessive salt intake in the diet is the cardiovascular system. Excess dietary salt intake usually affects heart, blood vessels, and the kidneys. It is well documented recently that the effect of salt on BP and BP independent target organ damage goes beyond the well-known concept of Guyton 27). Until recently, salt sensitivity of blood pressure was thought to be the result of delayed salt excretion by kidney malfunction. According to the classic concept of Guyton26), high salt intake increases in circulating volume, which leads to a rise in perfusion pressure of the kidneys and a natriuresis that tends to restore the increased circulating volume to normal. This pressure-natriuresis mechanism prevents the increase in BP that could arise from transient increase of circulating volume. However, recent studies have added some new insights into the pathophysiologic mechanisms of salt sensitive hypertension and questioned the classic view of salt sensitivity. In this brief review, some new pieces of research related to salt sensitivity are presented 28).