Summary Several clinical and large population studies indicate that women are more sensitive to salt than men, however, the precise mechanisms by which the onset of sexual dimorphism manifests are not yet fully understood. Here, we evaluate recent epidemiological data and highlight current knowledge from studies investigating sex-specific mechanisms of salt-sensitive blood pressure (SSBP). Emerging evidence indicates that women of all ethnicities are more sensitive to salt than men, at all ages, both premenopausal and postmenopausal. However, menopause exacerbates the severity and prevalence of SSBP, suggesting that female sex chromosomes predispose and female sex hormones mitigate salt-sensitive blood pressure (SSBP). |
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Results from human and rodent studies support the contribution of enhanced and inappropriate activation of the aldosterone-ECMR (endothelial cell mineralocorticoid receptor) axis promoting vascular dysfunction in women. Increases in the adrenal response to angiotensin II, in association with increased ECMR expression and endothelial ENaC (epithelial sodium channel) activation in women compared to men, are emerging as central players in the development of endothelial dysfunction and SSBP. in women. Female sex increases the prevalence and susceptibility of SSBP, and sex hormones and sex chromosome complement may exert antagonistic effects on the development of female SSBP.
Women of all ages and sexes have more salt-sensitive hypertension than men
There is growing evidence that women of all ethnicities and ages are more sensitive to salt than men, and that this propensity to retain more salt, which raises blood pressure, increases after menopause.
Another important emerging result is that healthy blood pressures may differ between the sexes, meaning that women could benefit from earlier, different intervention to prevent damage to the heart and vasculature.
“The reality is that women and men regulate our blood pressure differently and our blood pressures are different at the start of the study,” says Dr. Eric Belin de Chantemele, a physiologist at the Center for Vascular Biology at the School of Medicine. Georgia at Augusta University.
Women are generally thought to be better protected against cardiovascular disease than men until menopause, when the risk is thought to level off. Laboratory studies in traditional rat models of hypertension, such as the salt-sensitive Dahl rat, have generally supported those ideas, including an equalization of risk in the two sexes after ovarian removal.
But in female humans and some mouse models, the protection appears less absolute: because more women are sensitive to salt before menopause, and menopause exacerbates both its severity and prevalence, MCG scientists report in a paper review article that appears on the cover of the American Heart Association’s Hypertension magazine.
That supports another emerging concept that the XX sex chromosome predisposes women to salt sensitivity, presumably because women need to nearly double their fluid volume during pregnancy, and estrogen does help mitigate some of the related increased risk. , at least until your levels drop after menopause, says Belin de Chantemele.
Work primarily in male humans and animal models fuels the misconception that women are less sensitive to salt, write Belin de Chantemele and colleagues Dr. Jessica Faulkner, a vascular physiologist in the MCG Department of Physiology and a student of AU graduate Candee T. Barris.
“Salt sensitivity is one of the main factors of hypertension. And, if you look at people who have treatment-resistant hypertension, which is most people, most are sensitive to salt,” says Belin de Chantemele. “It is very important to know the cause of that.”
Salt sensitivity means that your body has an apparent natural tendency to retain salt instead of excreting the excess in urine.
Blood pressure salt sensitivity occurs when blood pressure decreases or increases more than 10% in response to the amount of salt you consume, scientists say.
Salt sensitivity is a factor in about half of cases where the cause of hypertension is not obvious, such as a kidney problem. It is also a common contributor to treatment-resistant hypertension, and only 1 in 4 adults has hypertension under control, according to the Centers for Disease Control and Prevention.
There is also good human data that reducing salt consumption reduces salt sensitivity and even more so in women, says Belin de Chantemele.
“We think it is primarily the vasculature not relaxing in response to a sodium intake that leads to an elevation in pressure,” she says of women’s distinctive salt management. Animal studies on salt sensitivity generally indicate that the kidneys, which should excrete more sodium when we consume too much, work well in females. In fact, human and lab animal evidence indicates that female kidneys are better at excreting salt, she says. The problem, it seems, is with the vasculature, because salt should also cause blood vessels to relax.
“If you expand your blood vessels more, you’ll be able to keep your blood pressure stable, but if your vessels don’t relax, that’s how the pressure goes up,” says Belin de Chantemele. “Later, it also excretes sodium to reduce blood volume, but the first response should be relaxation of the blood vessels.” And that’s how it works for those of us who are resistant to salt. But apparently not so well in many women.
One of the other unique factors about women that Belin de Chantemele and others are finding seems important is that, probably also because their bodies are primed to reproduce, they have high levels of the hormone aldosterone. Aldosterone is produced by the adrenal gland and has a direct effect on blood pressure by regulating the salt water balance in the body. Women also tend to have many more receptors for aldosterone, called mineralocorticoid receptors.
High levels of aldosterone are known to contribute to negative health effects, such as widespread inflammation, stiff and scarred blood vessels, and even an enlarged heart. In women, scientists think and have some evidence that aldosterone is primarily harmful to blood vessels, including their important ability to dilate to accommodate more blood volume in response to retaining more salt. Scientists see this effect in their laboratory mice and in women.
“We think what’s happening is that salt-sensitive women can’t reduce their aldosterone production enough, and we think that predisposes them to salt sensitivity,” says Belin de Chantemele.
Greater activation of the epithelial sodium channel, which causes the body to retain more salt, is another negative for women. And, the renin-angiotensin-aldosterone system, which coordinates the work of the heart, blood vessels and kidneys, to regulate fluid and electrolyte balance in the body, also tends to be suppressed in women.
There are drugs that target aldosterone, including the old blood pressure drug spironolactone, as well as newer drugs like eplerenone and finerenone, which Belin de Chantemele has studied in the lab and which he says would be a good first-line treatment for women because they reduce the action of aldosterone. He notes that drugs are gaining ground recently.
One of the many activities of MCG scientists is to see if aldosterone and estrogen levels have a connection, but they have no evidence of one at this time.
Important to the combination of a better understanding of sex differences in the way men and women regulate blood pressure is the emerging reality that, while women’s blood pressure tends to be lower than that of men Men, that doesn’t necessarily mean your pressures are good. Because while current guidelines have the same healthy blood pressure range for both sexes, it appears that women experience harm at a lower threshold or pressure.
Women tend to start with a lower pressure, so it is assumed that they are not hypertensive but, particularly after menopause , pressure increases can be much greater for women, says Belin de Chantemele.
“I would say the threshold for hypertension should be lower in women,” he says.
“If we had a different threshold , we would notice changes in pressure more quickly, so we could hopefully intervene more quickly.” And when blood pressure starts to rise, treatment for women should probably start with a lower pressure, she says.
While salt sensitivity is prevalent in both sexes and different ethnicities, large population studies around the world indicate that it is more common in women.
For example, large studies in China indicate that women have the greatest blood pressure response, up and down, to changes in dietary salt levels. Large studies of people in the United States, France, Spain, and Mexico also indicate that salt sensitivity is significantly more common in women. They note that people of African American descent have the highest overall incidence, regardless of sex, at 70%.
The two sex chromosomes, XX which makes a female and XY which means male, as well as sex hormones such as estrogen, are likely the key to women’s propensity for this common condition. Genetics, such as variations in the estrogen receptor, probably also contribute.
Evidence also indicates that women tend to like salt more than men, says Belin de Chantemele. Like many sex-related differences, salt propensity is probably related to the physiological need to retain sodium and the fluid that follows sodium, which is sufficient to sustain another life during pregnancy. There is also some evidence that the male hormone testosterone suppresses the appetite for salt.
Mouse models that have been found to spontaneously develop salt-sensitive hypertension might be better for future studies of this condition in females than older models such as the Dahl salt-sensitive rat, they write. Because what many have demonstrated time and time again in rats does not reproduce what happens with women, says Belin de Chantemele.
He also suggests that we all stop consuming salt. “It doesn’t get any better than that,” she notes.
