for millions of years , daily salt ( sodium chloride ) intake in man was about 1 g . then recently , about 10,000 years ago , salt intake increased by about ten - fold   because of the practice of using salt as a food preservative . it allowed former nomads to settle , grow grain and preserve foodstuffs over long periods . over the last few millennia , humans got used to the taste of salt and enjoyed the benefits of non - perishable food . genetically , humans are well - equipped with mechanisms that retain even tiny amounts of salt , a prerequisite for survival at those times when salt was scarce and intake was low . in keeping with this background , humans have less efficient excretory mechanisms when challenged with large salt loads , and the limiting factor is the rate of renal salt excretion . if salt intake exceeds the kidneys ability for salt excretion , then salt is deposited in the body , which , in synergy with aldosterone , affects heart , blood vessels   and kidneys . it is estimated that at least 30% of the world 's population develop hypertension ( elevated blood pressure ) when exposed to a high salt diet . in the past , salt sensitivity was thought to be the result of kidney malfunction , i.e. on the imbalance between salt input and salt output . however , recent observations suggest that the vascular system may also play an important role in this imbalance . more than 20 years ago , it was shown that the vascular endothelium expresses sodium channels similar to those in renal epithelia . some years later , it was demonstrated that sodium channel function in endothelium was regulated , much as it is in the kidney , by the mineralocorticoid hormone aldosterone . the fact that the vascular system is also a potential target for aldosterone led to a paradigm shift in so far as the attention was no longer directed solely to the kidney but also to the vascular system [ 13 - 20 ] . currently , there are far more data on the pathophysiology of aldosterone affecting vascular function than on the  normal  vascular physiology of this steroid hormone [ 21 - 33 ] . sodium and aldosterone synergistically act on the endothelium . at cellular level , small changes in plasma sodium concentration can have a large impact on endothelial function as long as aldosterone ( or aldosterone receptor function ) is available . even a 5% increase in plasma sodium concentration mechanically stiffens endothelial cells by about 25% , leading to cellular dysfunction ( decreased nitric oxide release / increased vascular smooth muscle tone ) . a major component of this high sodium sensitivity is the sodium channel in the endothelial plasma membrane , which is identical to the epithelial sodium channel cloned from renal tissue . this channel allows sodium to enter the endothelial cells   and , by yet unknown mechanisms , turn off endothelial nitric oxide synthase activity . do these in vitro experiments translate into the in vivo setting and explain how plasma sodium as such affects blood pressure ? this question is not easy to answer since changes in plasma sodium are usually accompanied by changes in osmolality , which may mask any direct action of sodium . however , a recent study properly corrected for any changes in osmolality , shows that there is indeed a marked alteration in blood pressure observable when plasma sodium is manipulated . similarly , blood pressure in dialysis patients is known to decrease when sodium concentration in the dialysate is lowered . furthermore , small but significant changes in plasma sodium , paralleled by concomitant changes in blood pressure , are known to occur in humans during acute or chronic salt intake . finally , there is experimental evidence that the brain may be involved in the sodium - triggered increase of blood pressure . blaustein and colleagues postulated an interesting hypothesis , namely that high sodium in the cerebrospinal fluid triggers the secretion of endogenous ouabain in the hypothalamus and suprarenal glands . endogenous ouabain acts in the brain , increasing sympathetic nerve activity , but also acts on blood vessels . both endogenous ouabain actions lead to vasoconstriction and increase in blood pressure . for obvious reasons , this more complex mechanism , involving different organs , most recently , the endothelial surface layer facing the blood stream has become a focus of interest [ 46 - 54 ] . this soft layer , termed endothelial glycocalyx , is a negatively charged biopolymer known to preferentially bind sodium . it has been calculated that about 700 mg of sodium can be transiently bound to the endothelial glycocalyx in the human body , which is about the amount contained in a single meal . interestingly , the sodium buffering capacity of the endothelial glycocalyx is severely damaged by excessive sodium intake over time , leading to a significant reduction of the negatively charged heparan sulphate residues in the endothelial glycocalyx . these observations led to a new concept of vascular sodium permeability , namely that two ( more or less ) permeable barriers determine the rate of sodium elimination after a salty meal . one barrier is the endothelial plasma membrane , with a variable sodium permeability depending on the abundance of epithelial sodium channels . the other barrier , located on the surface of the endothelium , is the endothelial glycocalyx that transiently buffers ingested sodium   and , thus , controls access to the epithelial sodium channels ( figure 1 ) . sodium channel activity and glycocalyx function are inversely related to each other . a plasma sodium concentration in the high - physiological range ( > 140 mm ) reduces the negatively charged heparan sulphate residues of the endothelial glycocalyx , increasing the amount of sodium reaching the endothelial sodium channels , which in turn makes the channels more active . the overall effect is that the barrier against sodium entry fails under these conditions and the endothelium becomes more permeable to sodium ( figure 2 ) . as indicated above , evidence for a salt - sensitive endothelial glycocalyx and its relationship to endothelial epithelial sodium channels is based on in vitro experiments and , at best , on ex vivo studies in human tissue ( e.g. human umbilical veins ) . to our knowledge , there are no direct studies in humans . however , if aldosterone is viewed as a hormone that facilitates sodium retention and epithelial sodium channel expression in the vascular endothelium , then a link between salt and glycocalyx , albeit indirect , becomes visible . clinical research often describes potentially important phenomena in the human without a mechanistic model . in this case , a mechanistic model based on in vitro experiments is available first , and it will be up to clinical research to test it in the human . this state of vascular function is associated with low daily sodium intake , and/or low aldosterone and/or favorable genetics . this state of vascular function is associated with high daily sodium intake , and/or high aldosterone and/or unfavorable genetics . after a salty meal , the translocation of sodium from the blood into the interstitium is delayed by the significant buffering capacity of the endothelial glycocalyx . sodium will reversibly bind to / dissociate from the endothelial glycocalyx binding sites and , thus , can be readily excreted via the kidneys . excessive sodium intake over time will damage the endothelial glycocalyx and lead to a decrease in its sodium buffering capacity because of the loss of negatively charged heparan sulphate residues . following that , sodium gains direct access to the " unprotected " epithelial sodium channels . thus , in addition to the paracellular transport route ( i.e. sodium transport between endothelial cells along its chemical gradient ) , sodium uses the transcellular pathway for entering the large extracellular space ( about 30% of body weight ) . there , sodium is bound reversibly to the extracellular matrix [ 59 - 63 ] . after the ingested sodium has spread throughout the body , the plasma sodium concentration decreases . now , sodium starts diffusing back into the vascular bed ( along its chemical gradient directed from interstitium to blood ) and will finally be excreted by the kidneys ( figure 2 ) . this  detour of sodium " through the whole organism delays renal sodium excretion significantly . in the meantime , a sodium load from the next salty meal may arrive and so on , leading over time to sodium accumulation in the organism . vascular salt sensitivity can be defined as the ratio of " endothelial sodium channel activity over endothelial glycocalyx sodium buffer capacity " . it should be noted that vascular salt sensitivity is not thought to be exclusively  congenital  [ 8,64 - 66 ] but could most likely be influenced ( among other yet - unknown factors ) by the amount of ingested salt and by endogenous aldosterone . as salt sensitivity correlates positively with sodium channel activity in the endothelium , the blockade of these channels by amiloride analogues should help in identifying individuals with a high sensitivity to salt . the test is described in general terms in figure 3 ( see figure legend and , for more details , see ) . the four cylinders symbolize the vascular system . after an acute na load ( 5 g nacl orally ) , with and without addition of an epithelial sodium channel blocker ( two separate sessions ) , blood pressure low vascular sensitivity is indicated by a  ~ zero , high vascular sensitivity is indicated by a  > zero . the endothelial glycocalyx appears to be a key structure for regulating body sodium . in vitro studies show that the quality of this biopolymer layer is determined by the abundance of its electrical negative charges . loss of these surface charges renders the endothelial surface vulnerable to unwanted intruders , among them excessive sodium . we look forward to clinical research that will hopefully confirm these results in vivo in humans and substantiate the mechanism behind the protective effect of a low salt diet on the cardiovascular system .
excessive amounts of salt in food , as usually consumed worldwide , affect the vascular system , leading to high blood pressure and premature disabilities . 
 salt entering the vascular bed after a salty meal is transiently bound to the endothelial glycocalyx , a negatively charged biopolymer lining the inner surface of the blood vessels . 
 this barrier protects the endothelium against salt overload . 
 a poorly - developed glycocalyx increases the salt permeability of the vascular system and the amount of salt being deposited in the body , which affects organ function . 
 a simple test system is now available that evaluates vascular salt sensitivity in humans and identifies individuals who are at risk of salt - induced hypertension . 
 this short review aims to discuss how the underlying basic research can be translated into medical practice and , thus , meaningful health outcomes .