Sodium intake and vessel wall properties of large arteries

There is evidence that high sodium intake may influence the cardiovascular system in hypertensive subjects related to but also independent of blood pressure changes [1,2]. In this issue of the journal, Simon et al. [3] present a prospective animal study investigating the effect of a long-term high-sodium diet on structural and mechanical properties of the carotid and mesenteric arteries in adult male Sprague–Dawley rats. When compared to the control group on low-sodium, after a high- sodium diet, there was a dilatation of the carotid and mesenteric arteries, although blood pressure levels remained in the normal range and did not differ between the low- and high-sodium groups. In the carotid artery, a compensatory remodelling with a normalization of lumen area was observed after 6 months of high-sodium diet, which was associated with an unchanged carotid artery distensibility. In the mesenteric arteries, there was dilatation without compensatory remodelling, therefore leading to reduced arterial distensibility. The data of Simon et al. [3] show that high-sodium diet can lead to structural and distensibility changes of arteries in Sprague–Dawley rats, even in the absence of sodium-induced changes in blood pressure. Both carotid and mesenteric arteries showed a dilatation with the high sodium diet. However, when compensatory remodelling was observed, as suggested by a normalization of lumen area in the carotid arteries, no change of arterial distensibility occurred. For many years, numerous studies evaluated the complex relationships between sodium intake and blood pressure and the possible effects of sodium on the pathophysiology of arterial hypertension [4,5]. Most of these studies were based on the concept that, in early stages, high-sodium intake leads to an increase in cardiac output causing high blood pressure, followed by an increase in vascular resistance in late stages. Accordingly, it has been emphasized that alterations of the arterioles are the main consequence of high sodium load. However, the possibility that sodium could exert adverse effects on the entire cardiovascular system, and that these alterations may develop independently of blood pressure elevation, has only recently been considered. The study by Simon et al. [3] suggests that high-sodium intake can result in structural and mechanical vessel wall properties of large arteries without a change in blood pressure. These data show that the effects of sodium on arterial stiffness cannot be related to a simple mechanical effect of increased distending pressure. It is well known that sodium can modify vascular muscle tone by mechanisms involving the sympathetic nervous system [6], the calcium exchange, insulin sensitivity [7] and neurohumoral as well as endothelium-dependent factors [5,8]. Increased vascular muscle tone, resulting from sympathetic stimulation, has been shown to affect not only the arterioles, but also the elastic properties of large arteries [9–12] implicating that sodium can also modify arterial stiffness. In rat models, hypertrophy is associated with arterial stiffness, particularly in elderly animals [13]. Limas et al. [14] showed that sodium load can induce a significant thickening of the aortic media and an excessive collagen production in spontaneously hypertensive rats within 5 weeks, although blood pressure was not affected during a sodium load for at least 11 weeks. In salt-sensitive Dahl rats that were fed either with a low- or high-sodium diet for 5 weeks, the stiffness of the carotid arteries was increased in both diet groups compared to salt-resistant rats [15]. These data suggest that sodium sensitivity is an important factor for the development of arterial stiffness in the presence of a high-sodium load. Taken together, the existing experimental rat models and the data of Simon et al. [3] demonstrate pressure-independent effects of sodium on structural and functional vessel wall properties of large arteries. Genetic factors, particularly those involved in sodium sensitivity, appear to play a permissive role for sodium-induced vessel wall alterations. However, these are also observed in genetic models not prone to sodium-induced increases in blood pressure. A higher sensitivity of systolic pressure to sodium was described in elderly patients, particularly in sodium-sensitive patients, which can be attributed to a sodium-induced increase in the rigidity of the arterial wall [16,17]. An intravenous administration of isotonic saline induced an increase in systolic blood pressure with no change in diastolic blood pressure, together with a significant reduction of arterial compliance. This suggests that decreased arterial compliance after saline infusion is related to sodium-induced mechanisms acting on the arterial wall rather than to increased distending blood pressure [18]. Draaijer et al. [19] showed that the compliance of the carotid, brachial and femoral arteries was reduced in sodium-sensitive borderline hypertensive subjects compared to salt-resistant borderline hypertensive subjects with similar blood pressure and vascular resistance. They also emphasized the role of genetic factors, particularly those related to sodium sensitivity, for the development of sodium-induced arterial vessel wall changes. An effect of sodium on large arteries was also observed in normotensive, healthy subjects. Avolio et al. [20] investigated the pulse-wave velocity in normotensive subjects on low-sodium diet and on regular sodium diet matched for age and blood pressure. In the low-salt group pulse-wave velocity in the aorta, arms and legs was significantly lower compared to the control group on a regular sodium diet. The results of their study demonstrate that arterial stiffness is lower in normotensive subjects who are on a low-salt diet. Interestingly, in a study by Simon et al. [3], remodelling of the arterial wall compensated for the loss of distensibility induced by arterial dilatation. These data confirm the results of human studies involving dynamic assessment of elastic arterial wall properties in vivo, where it was shown that, in hypertensive patients, arterial remodelling with wall thickening may partly compensate hypertension-induced losses of distensibility [10,21]. In contrast, patients with renal failure had severe structural alterations of the arterial wall and arterial dilatation was associated with loss of distensibility [22]. The effects of sodium on large arterial structure and function has important implications. In Western countries, the usual sodium intake exceeding 150 mmol per day is very high and affects the vast majority of the population [23]. In salt-sensitive subjects, or in subjects with a genetic predisposition, sodium can induce structural vessel wall changes, which are associated with arterial stiffening. An obvious consequence of arterial stiffening [24] is the early return of wave reflections to the aorta as a consequence of increased pulse wave velocity. Early return of wave reflection from the periphery of the body is the reason for the disappearance of the reflected wave from diastole and its movement into systole, leading to increased systolic and pulse pressure at the expense of mean diastolic pressure, which decreases. These haemodynamic alterations lead to left ventricular hypertrophy [25] and to a compromised coronary perfusion [26]. Moreover, it was demonstrated that isolated systolic hypertension and pulse pressure are independent cardiovascular risk factors [27]. Taken together, it appears reasonable to assume that the high sodium load in Western countries is associated with an increased cardiovascular morbidity and mortality, which is not only related to its effects on blood pressure.