Review Article
Salt and essential hypertension: pathophysiology and implications for treatment

https://doi.org/10.1016/j.jash.2017.04.006Get rights and content

Highlights

  • High salt intake increases blood pressure in some individuals.

  • Factors that impair urinary sodium secretion are risk factors for hypertension.

  • Hypertension may be a physiological response to excrete excess salt.

  • Natriuresis is required for effective long-term pharmacotherapy of hypertension.

Abstract

Essential hypertension is common and is associated with significant morbidity and mortality. However, questions remain as to the exact physiological mechanisms underlying this disease. First, we discuss how essential hypertension may be largely a result of a maladaptation to a high-salt diet and that high blood pressure, rather than being an inactive side effect of high salt intake, may be an adaptive mechanism to improve salt secretion. Next, we explain how any physiological state that reduces urinary sodium concentrating ability may increase an individual's risk for salt-induced hypertension. Finally, we conclude that natriuresis is a crucial criterion for effective long-term pharmacologic treatment of essential hypertension.

Introduction

Hypertension affects approximately 40% of the world population aged >25 years1 and has been estimated to cause 10.4 million deaths worldwide per year.2 Essential hypertension is defined as an elevated blood pressure where “secondary” causes of hypertension, such as renovascular disease or Cushing's disease, have been ruled out. This is not to say that essential hypertension does not have a root cause. In the following paragraphs, the role of elevated salt intake as a major causative factor behind this disease will be explored. Furthermore, how certain key factors (age, African descent, chronic kidney disease [CKD], and low potassium intake) contribute to its pathogenesis by interacting with dietary salt will be considered. Finally, we explore the implications for the pharmacologic treatment of this disease.

Section snippets

Salt Causes Hypertension

Humans currently consume much more salt than for which the species may be evolutionarily suited. It has been theorized that Paleolithic man consumed approximately 0.69 g of sodium per day.3 In comparison, the average present day human consumes approximately 4.9 g of sodium per day.4 This change in salt intake likely occurred <10,000 years ago with the advent of salt extraction technology,5 and it is unlikely that the human race has had enough time, on an evolutionary time scale, to have adapted

Hypertension Enhances Renal Salt Secretion

A kidney programmed for a low-salt diet but experiencing a high-salt diet may have difficulty excreting the excess salt. Indeed, a recent review of human salt loading trials showed a statistically significant increase in serum sodium concentration across both normotensive and hypertensive groups in the majority of the studies reviewed.13 The study of the longest duration was performed in 17 normotensive and 23 hypertensive subjects who were sequentially randomized to one of four levels of

Mechanisms of Blood Pressure Rise

How does the body sense excess salt and raise blood pressure? Early theories centered on increased plasma volume: sodium retention was thought to lead to increased serum sodium leading to increased thirst and plasma volume. This would then result in increased cardiac index and increased blood pressure. However, although cardiac index may initially rise in the setting of salt loading, this will usually return to normal while total peripheral resistance (TPR) will rise and remain elevated, at

Risk Factors for Salt-induced Hypertension

In the face of increased sodium intake, some individuals will maintain constant blood pressure, whereas others will demonstrate salt sensitivity and an increase in mean arterial pressure. This phenomenon may explain the wide variation in dietary salt to blood pressure response in observational and salt loading trials. In fact, one interventional salt loading study in healthy normotensive male volunteers found individual blood pressure increases ranging from 1.5% to 34%.26

Why this variation in

Implications for Treatment

If essential hypertension is a direct result of salt retention, as has been discussed in this article, any intervention that either decreases salt intake or increases salt excretion will lower blood pressure. An obvious first step in the management of the hypertensive patient should be lifestyle modification. If this fails, pharmacologic treatment can be considered.

Lifestyle modification includes dietary changes to restrict salt and increase potassium intake, such as the low-sodium DASH diet.42

Conclusions

It is important to be cognizant of evolutionary history. Essential hypertension may be the result of a human maladaptation to an increase in dietary salt intake and a decrease in dietary potassium intake that are recent on an evolutionary time scale. When renal sodium mechanisms are overwhelmed, the body responds by raising blood pressure to enhance urinary sodium excretion. However, this becomes maladaptive in the long run by increasing the risk of cardiovascular disease. Any physiological

Acknowledgments

The author would like to thank Dr Norman Campbell and Dr Sophia Chou for their help with reviewing the article.

References (52)

  • F. Luca et al.

    Evolutionary adaptations to dietary changes

    Annu Rev Nutr

    (2010)
  • L.K. Dahl

    Possible role of salt intake in the development of essential hypertension. 1960

    Int J Epidemiol

    (2005)
  • INTERSALT: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. INTERSALT Cooperative Research Group

    BMJ

    (1988)
  • N.R. Poulter et al.

    The Kenyan Luo migration study: observations on the initiation of a rise in blood pressure

    BMJ

    (1990)
  • D. Simmons et al.

    Blood pressure and salt intake in Malawi: an urban rural study

    J Epidemiol Community Health

    (1986)
  • N.J. Aburto et al.

    Effect of lower sodium intake on health: systematic review and meta-analyses

    BMJ

    (2013)
  • H.E. de Wardener et al.

    Plasma sodium and hypertension

    Kidney Int

    (2004)
  • A.G. Johnson et al.

    Blood pressure is linked to salt intake and modulated by the angiotensinogen gene in normotensive and hypertensive elderly subjects

    J Hypertens

    (2001)
  • H. Shimamoto et al.

    Time course of hemodynamic responses to sodium in elderly hypertensive patients

    Hypertension

    (1990)
  • R.C. Tarazi et al.

    Plasma volume in men with essential hypertension

    N Engl J Med

    (1968)
  • T. Linde et al.

    Blood viscosity and peripheral vascular resistance in patients with untreated essential hypertension

    J Hypertens

    (1993)
  • H. Oberleithner et al.

    Plasma sodium stiffens vascular endothelium and reduces nitric oxide release

    Proc Natl Acad Sci U S A

    (2007)
  • S.D. Stocker et al.

    Neurogenic and sympathoexcitatory actions of NaCl in hypertension

    Curr Hypertens Rep

    (2013)
  • O.V. Fedorova et al.

    Brain ouabain stimulates peripheral marinobufagenin via angiotensin II signalling in NaCl-loaded Dahl-S rats

    J Hypertens

    (2005)
  • A.Y. Bagrov et al.

    Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets

    Pharmacol Rev

    (2009)
  • A.Y. Bagrov et al.

    Effects of two putative endogenous digitalis-like factors, marinobufagenin and ouabain, on the Na+, K+-pump in human mesenteric arteries

    J Hypertens

    (1998)
  • Cited by (50)

    • Therapeutic aspect of microRNA inhibition in various types of hypertension and hypertensive complications

      2022, Gene Reports
      Citation Excerpt :

      Essential hypertension (EH) continues to be a key modifiable risk factor for cardiovascular disease (CVD) and has indeed been major public health concern due to its link to an enhanced danger of certain vascular disorders such as myocardial infarction and stroke etc. Evidences suggested that genetic factors play a role in the severity of EH (Carretero and Oparil, 2000a, 2000b; Garfinkle, 2017). Interestingly, in response to cardiac stress, miR-21 was upregulated, and inhibiting it with an antagomiR was shown to prevent cardiac hypertrophy and fibrosis in rodents.

    • Food and salt structure design for salt reducing

      2021, Innovative Food Science and Emerging Technologies
      Citation Excerpt :

      Sodium chloride is also known as common salt and is widely applied in processed foods (Steffensen et al., 2018). It is well recognized that a high-salt diet increases the mortality and incidence of cardiovascular diseases (CVDs), such as high blood pressure (Garfinkle, 2017), and coronary heart diseases (Xue et al., 2020). The cardiovascular disease was supposed to be the major cause of diet-related deaths (10 million deaths) and disability-adjusted life-years (DALYs) (207 million DALYs), which is particularly true for countries like China, Japan, and Thailand (Afshin et al., 2019).

    View all citing articles on Scopus

    Conflicts of interest: We declare no conflicts of interest or sources of funding.

    View full text