An alternative hypothesis to the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension

Abstract

It is widely held that in response to high salt diets, normal individuals are acutely and chronically resistant to salt-induced hypertension because they rapidly excrete salt and retain little of it so that their blood volume, and therefore blood pressure, does not increase. Conversely, it is also widely held that salt-sensitive individuals develop salt-induced hypertension because of an impaired renal capacity to excrete salt that causes greater salt retention and blood volume expansion than that which occurs in normal salt-resistant individuals. Here we review results of both acute and chronic salt-loading studies that have compared salt-induced changes in sodium retention and blood volume between normal subjects (salt-resistant normotensive controls) and salt-sensitive subjects. The results of properly controlled studies strongly support an alternative view: during acute or chronic increases in salt intake, normal salt-resistant subjects undergo substantial salt retention and do not excrete salt more rapidly, retain less sodium, or undergo lesser blood volume expansion than do salt-sensitive subjects. These observations: 1) directly conflict with the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension, and 2) have implications for contemporary understanding of how various genetic, immunologic, and other factors determine acute and chronic blood pressure responses to high salt diets.

Tissue Sodium Content and Arterial Hypertension in Obese Adolescents

“…Salt-loading studies with salt-resistant subjects have shown that, during acute or chronic salt-loading, normotensive salt-resistant subjects do not excrete Na + faster, nor do they experience more blood volume expansion. Instead, they substantially retain Na + in a rhythmical manner, which is in line with our concept of relevant tissue Na + buffers [24,25]. Impairment of these buffer mechanisms in our "early disease stage" study could be an important contributor to the onset of arterial hypertension: while, in obese young patients without hypertension, Na + storage in the muscle (the largest previously described buffer compartment) is only slightly reduced, in those with hypertension we observed an accentuated reduction of Na + storage in muscle.…”

An Appraisal of Methods Recently Recommended for Testing Salt Sensitivity of Blood Pressure

“…The mechanisms of salt sensitivity are the subject of ongoing controversy and discussion . Whereas a considerable degree of controversy stems from differing views on the interpretation of specific studies or theories, it can also be related to differences between the methods used to identify subjects with salt sensitivity.…”

“…The mechanisms of salt sensitivity are the subject of ongoing controversy and discussion. 1,29,[43][44][45][46][47][48][49][50][51][52] Whereas a considerable degree of controversy stems from differing views on the interpretation of specific studies or theories, it can also be related to differences between the methods used to identify subjects with salt sensitivity. For example, studies with the furosemide-based protocol indicate that during the salt restriction phase, salt-sensitive hypertensive subjects undergo similar or greater increases in plasma catecholamines than do salt-resistant hypertensive subjects.…”

Early urinary biomarkers of renal tubular damage by a high‐salt intake independent of blood pressure in normotensive rats

“…Dietary sodium intake has been associated with progression to chronic kidney disease (CKD) and cerebrovascular disease (CVD) as well as hypertension. In response to a high‐salt intake, normal individuals are acutely and chronically resistant to salt‐induced hypertension because they rapidly excrete salt and retain little of it so that their blood volume, and therefore blood pressure (BP), does not increase . However, a high salt intake causes marked organ damage without an increase in BP in normal humans .…”

“…In response to a high-salt intake, normal individuals are acutely and chronically resistant to salt-induced hypertension because they rapidly excrete salt and retain little of it so that their blood volume, and therefore blood pressure (BP), does not increase. 1 However, a high salt intake causes marked organ damage without an increase in BP in normal humans. 2 It was also shown that the arterial pressure did not elevate in normotensive rats exposed to salt overload, but they developed an increase in the left ventricular (LV) mass, LV remodeling, and cardiac and renal fibrosis.…”