engleski

Endothelial dysfunction and salt intake in early stages of hypertension

Long-term increased dietary salt intake commonly leads to an increase in arterial blood pressure (BP), that results in development of hypertension. This makes high salt (HS) intake, which is present in almost all parts of the world, an emerging risk factor for increased cardiovascular, cerebrovascular and renal morbidity and mortality. However, in a last few decades, it became evident that HS intake can induce significant organ damage and increase the risk for early morbidity and mortality even in the absence of arterial BP changes. A number of studies have demonstrated that such early manifested and BP-independent effect of HS loading presents development of endothelial dysfunction (ED), which has been denoted as a precursor and the earliest detectable outcome of various cardiovascular diseases (CVDs). In order to elucidate the effects of dietary HS intake on vascular and endothelial function, studies traditionally investigated rodents (primary rats). Results of these studies demonstrated that changes in HS intake significantly alter vascular reactivity in different vascular beds and in response to various stimuli (even in normotensive animals), probably due to ED which was shown to be associated with low levels of angiotensin II (ANG II) and increased oxidative stress. The earliest clinical (human) studies that investigated the effects of HS loading on vascular/endothelial function were predominantly performed in hypertensive patients, and therefore were not been able to separate the effects of HS diet on endothelium from the effect of elevated BP. Thus, it was necessary to start investigating the vascular responses to salt loading in healthy, normotensive individuals as well. The earliest studies in healthy individuals brought conflicting results ; while some authors reported that short-term HS loading impairs endothelial function in both macro- and microcirculation (venous occlusion plethysmography, peripheral arterial tonometry, flow mediated dilation), others failed to demonstrate such effect. However, several later studies have more clearly demonstrated the deleterious effect of HS loading on endothelium that is independent of the changes in arterial BP in healthy individuals. Moreover, some of these studies took step forward in order to investigate at least part of mechanisms mediating HS-induced changes of endothelial function, including its effect of renin- angiotensin system (RAS), oxidative stress, fluid retention, sex-related differences etc. One study demonstrated that HS intake-induced impairments in cutaneous vasodilatation were improved by the local infusion of ascorbic acid, suggesting a role for oxidative stress in contributing to vascular impairment. Moreover, it was reported that 7-days HS loading did not induce significant changes in body composition and fluid status in healthy individuals, indicating that endothelial changes are independent of fluid retention, just as they are BP independent. Regarding possible gender differences in endothelial response to HS loading, it was suggested that men have a greater sensitivity of large conduit arteries to salt loading compared to age-matched women. Taken together, studies in healthy individuals have largely confirmed what has been learned from animal studies – short-term HS diet impairs endothelial function and vascular reactivity in both macro- and microcirculation independently of BP changes. Moreover, according to the latest results, studies in humans are beginning to give an insight into possible mechanisms (including suppression of RAS, oxidative stress, inflammation and endothelial-leukocyte interaction, adrenergic system activity, fluid retention, endothelial glycocalyx alterations, osmotically inactive sodium storage etc.), as well as gender-based differences in the effect of HS intake on endothelial function.

high-salt diet ; microcirculation ; endothelium ; macrocirculation

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