Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction

Abstract

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. With the recent large increase of dietary salt intake in most developed countries, the prevalence of hypertension increases tremendously which is about 30% of the world population. There is substantial evidence that suggests some people can effectively excrete high dietary salt intake without an increase in arterial BP, and another people cannot excrete effectively without an increase in arterial BP. Salt sensitivity of BP refers to the BP responses for changes in dietary salt intake to produce meaningful BP increases or decreases. The underlying mechanisms that promote salt sensitivity are complex and range from genetic to environmental influences. The phenotype of salt sensitivity is therefore heterogeneous with multiple mechanisms that potentially link high salt intake to increases in blood pressure. Moreover, excess salt intake has functional and pathological effects on the vasculature that are independent of blood pressure. Epidemiologic data demonstrate the role of high dietary salt intake in mediating cardiovascular and renal morbidity and mortality. Almost five decades ago, Guyton and Coleman proposed that whenever arterial pressure is elevated, pressure natriuresis enhances the excretion of sodium and water until blood volume is reduced sufficiently to return arterial pressure to control values. According to this hypothesis, hypertension can develop only when something impairs the excretory ability of sodium in the kidney. However, recent studies suggest that nonosmotic salt accumulation in the skin interstitium and the endothelial dysfunction which might be caused by the deterioration of vascular endothelial glycocalyx layer (EGL) and the epithelial sodium channel on the endothelial luminal surface (EnNaC) also play an important role in nonosmotic storage of salt. These new concepts emphasize that sodium homeostasis and salt sensitivity seem to be related not only to the kidney malfunction but also to the endothelial dysfunction. Further investigations will be needed to assess the extent to which changes in the sodium buffering capacity of the skin interstitium and develop the treatment strategy for modulating the endothelial dysfunction.

The hypotensive effect of salt substitutes in stage 2 hypertension: a systematic review and meta-analysis

“…Notwithstanding, recent studies indicate that modification of endothelial cell function and non-osmotic storage of salt could be the result of changes in endothelial surface layer characteristics. Therefore, it seems that, in addition to kidney malfunction, endothelial dysfunction could be considered as an effective factor related to salt sensitivity and sodium homeostasis [52].…”

Enfermedades cardiovasculares, hipertensión arterial y consumo de sodio: una relación controversial / Cardiovascular diseases, high blood pressure and sodium intake: a controversial relationship

“…Alta ingesta de sodio, (excreción> 6g Na/día) Baja ingesta de sodio, (excreción <3g Na/día) (La reducción de la ingesta, solo aplicada a pacientes con HAS y dieta alta en Na). Sin embargo, diversos estudios han demostrado que no en todos los individuos un consumo de sal elevado se asocia con hipertensión (Young, C. H. et al, 2015), ni tampoco todos los sujetos responden de igual forma a la reducción de ingesta de sodio. Se ha sugerido que una dieta baja en sodio (3 g de sal Na/ d) podría ser más eficaz en la reducción de la PA en mujeres y ancianos (He, F. J. et al, 2009) y en sujetos de raza negra o asiática en comparación con la caucásica (Graudal N.A., 2012).…”

“…Los mecanismos subyacentes que promueven esta variabilidad son complejos y van desde la genética hasta influencias ambientales (Young, C. H., 2015).…”

Salt and Hypertension Hypothesis - Still Relevant

“…In addition to these, dietary sodium, or salt, intake has been found to play a key player, and the most common and important risk factor for hypertension. [3] Numerous clinical trials have shown a direct association and causal relation between salt intake and the pathogenesis of hypertension. In particular, sodium retention due to the overproduction of sodium-retaining hormones or inappropriate renal salt handling due to alterations in expression of the Kallikrein-Kinin system have been implicated as mechanisms in hypertension.…”