The Dietary Sodium-Blood Pressure Plot “Stiffens”

Abstract

N early 50% of our population by 65 years of age has a systolic pressure within a "risky" range, that is, has predominantly systolic hypertension (PSH), 1 attributable, in part, to a reduction in large artery compliance because of an increased stiffness of the arterial wall. For a given pattern of left ventricular ejection, arterial stiffening reduces diastolic pressure and increases pulse pressure. Although increased arterial stiffness elevates pulse pressure, it is not itself sufficient to raise systolic pressure to hypertensive levels, unless accompanied by an increase in stroke volume or peripheral vascular resistance (PVR). 2 Whereas the former is not increased in older persons with PSH, the latter is higher (by Ϸ15% on average) than in age-matched normotensive persons. 3 This mild-moderate elevation of PVR is usually unrecognized because it is not routinely assessed. The increased large artery stiffness that accompanies PSH precedes the elevation of arterial pressure to clinically defined hypertensive values, 4 giving rise to the notion that this form of hypertension, at least in part, is a disease of the arterial wall. Moreover, elevated pulse wave velocity, an index of arterial stiffness, and reduced total systemic compliance, assessed by stroke volume/pulse pressure, are themselves independent predictors of future cardiovascular events, even after accounting for the effect of the concomitant increase in blood pressure. 5,6 There is substantial evidence to indicate that the NaCl dependence of arterial pressure increases with advancing age and that this age effect is exaggerated in older hypertensive patients. 7 In this issue of Hypertension, Gates et al 8 add to this perspective by demonstrating that a reduction in dietary sodium to approximately 60 mmol/d, considered to be a low sodium intake by the Dietary Approaches to Stop Hypertension (DASH) study, 9 effectively lowers arterial pressure in older persons with PSH. Gates et al 8 also confirm prior observations that reducing dietary NaCl increases arterial compliance and reduces arterial stiffness. 10 Of particular note is that both the compliance and stiffness effects were evident 1 to 2 weeks following a reduction in NaCl. 8 Although PVR was not measured in their study, the Gates et al results demonstrate that reduction in dietary NaCl reduces diastolic as well as systolic pressure in PSH; pulse pressure is also reduced. 8 In addition to its effect on arterial pressure, NaCl affects arterial stiffness by altering vascular structure and smooth muscle cell and endothelial cell function. Both clinical and experimental evidence indicate that NaCl induces hypertrophy of the arterial wall in the absence of changes in arterial pressure 11 and induces hypertrophy of cultured vascular cells. 12 Excessive NaCl intake reduces the bioavailability of nitric oxide by interfering with the induction of nitric oxide synthase; by increasing asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, 13 reducing the production of nitric oxide; and by el...

Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness

“…166 Smooth muscle tone also increases because of endogenous Na pump ligands such as marinobufagenin or ouabain-like substances that increase with high-salt intake. 81 Among the pharmacological approaches for reducing vascular stiffness and/or its cardiac effects, diuretics, nitrates, and RAAS inhibitors are most commonly used. Although providing some usefulness, these agents have not solved the problem, and there remains a serious lack of effective therapies that directly target the structural abnormalities and changes in vascular signaling that underlie stiffening.…”

“…79 Dietary salt augments vascular stiffness with increasing age, and low-sodium diets consumed by older adults improve arterial compliance. 80,81 In response to NaCl, VSMC tone is stimulated and vascular wall composition altered with a marked increase in the medial layer with VSMC hypertrophy and abundant collagen and elastin production. [82][83][84][85] Salt intake interacts with genetic polymorphisms for genes such as angiotensin type I receptors, nitric oxide, and ALDO synthase.…”

“…86 -88 Sodium also impairs endothelial function by reducing the production of nitric oxide by NOS, thereby diminishing nitric oxide bioavailability and by stimulating NOS inhibitor asymmetrical dimethylarginine and enhancing NADPH oxidase activity. 81 This results in enhanced ROS stimulation as a common mechanism for arterial stiffening. …”

Genetic variations of tubular sodium reabsorption leading to “primary” hypertension: from gene polymorphism to clinical symptoms

“…First, the adducin effects on organ damage may be due to renal Na retention that may promote organ damage, per se, as it occurs in a high-salt diet (5,7). A slight increase in body sodium may favor the production of reactive oxygen species (4,33,102,123), a well-known mediator of organ damage.…”

Arterial Stiffness and Hypertension

“…7 Although controversial, the preponderance of evidence now favors dietary salt-induced arterial stiffness in association with hypertrophy of the arterial wall, alteration of the vascular endothelial cells, and upregulation of angiotensin II receptors, all in the absence of a change in BP. 8 Similarly, there are abundant animal and human studies showing salt-dependent development of arterial stiffness and left ventricular hypertrophy that is independent of an increase in BP. 9 The recent study by Sesso et al 10 has clearly shown that elevated plasma C-reactive protein was associated with the future development of hypertension in a dose-dependent manor.…”