Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension

Abstract

To examine the mechanisms underlying the sensitivity to sodium intake in a subset of patients with essential hypertension, we studied the effects of different sodium intake (10, 100, 200 mEq/day) on blood pressure, the function of the renin-angiotensin-aldosterone system, and on blood levels of catecholamines in 20 patients with essential hypertension and 10 normal subjects. Mean blood pressure (MBP) was not different in hypertensive and normal subjects during low sodium diet. But, with high sodium intake, MBP increased by at least 10% in 12 patients (salt-sensitive), whereas in the remaining 8 patients (salt-resistant) and in normal subjects, MBP did not change significantly. This phenomenon cannot be attributed to differences in sodium retention because the percent change in body weight ad the urinary sodium excretion in the salt-sensitive patients was not different than it was in salt-resistant patients or in normal subjects. The observed difference in blood pressure response to high sodium intake in salt-sensitive patients is also not dependent on an impaired suppressibility of the renin-angiotensin-aldosterone system because there were no significant differences in the basal levels of PRA and aldosterone between the groups, and because the orthostatic increments in PRA were significantly lower in salt sensitive than they were in the salt-resistant patients and in normal subjects. Plasma norepinephrine (NE) levels were not significantly different between normal subjects or hypertensive patients while on low sodium intake. But during high sodium intake, they decreased significantly (P less than 0.05) in normal subjects (from 22 +/- 3.4 to 12 +/- 2.3 ng/dl) and in salt-resistant patients (from 17 +/- 4.5 to 13 +/- 2.4 ng/dl) but not in salt-sensitive patients (from 20 +/- 1.9 to 22 +/- 3.2 ng/dl). Furthermore, the majority of salt-sensitive patients displayed inappropriately high plasma NE in relation to their urine excretion of sodium during high sodium intake. Finally, the increments in plasma NE after 5 min of standing were significantly greater in salt-sensitive patients than they were in salt-resistant patients and normal subjects during both low or high sodium intake. These data indicate that a subset of patients with essential hypertension may have impaired suppressibility of plasma NE during high sodium intake, which suggests hyperactivity of the sympathetic nervous system in these patients. These aberrations may be responsible for the increase in MBP in the salt-sensitive patients during high sodium intake.

Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors.

“…In this study we have also confirmed in white patients our previous observation in blacks 4 that salt-sensitive patients with essential hypertension display significant alterations of the renal hemodynamic adaptation to a high dietary NaQ intake. In salt-sensitive patients, a disturbance in the relative changes of the afferent and efferent renal vascular resistances during a high NaCl diet results in increased intra- glomerular pressure, which could cause greater amounts ofUAE.…”

Sodium sensitivity in human subjects. Hemodynamic and hormonal correlates.

“…Our studies did not show differences in plasma catecholamines in the four groups, especially in relation to salt intake, as suggested by Campese et al 7 Koolen and van Brummelen, 6 and Fujita et al," but at present we have no indirect suggestion that sympathetic nervous system activity differs between the two groups, as heart rate and cardiac index were not significantly different. We have no data relative to other vasoactive agents, such as vasopressin, prostaglandins, bradykinin, atrial natriuretic factor, renomedullary vaso-depressor lipids, or circulating inhibitors of Na + ,K + -adenosine triphosphatase (ATPase).…”

Hemodynamic and Autonomic Response to Different Salt Intakes in Normotensive Individuals

“…However, we also showed that during low‐salt diet the SS‐Index is positively associated with cardiac output and arterial compliance and negatively associated with SVR and characteristic impedance, suggesting a residual positive salt balance in SS subjects during salt depletion and giving support to Guyton's physiology. We may also hypothesize a role played by altered modulations of the renin–angiotensin–aldosterone system or of the sympathetic nervous system, reported to occur in hypertensive SS individuals 3, 27. However, studies in normotensive humans revealed that an increased dietary salt intake (5–7 days of high‐salt regimen) induces a profound reduction in vascular nitric oxide bioavailability, which limits endothelium‐dependent vasodilation 28, 29.…”

“…Sodium loading/depletion maneuvers may unveil alterations in cardiovascular control associated with sodium sensitivity possibly involved in the increased rate of cardiovascular events. In this regard, while it has been shown that salt‐sensitive hypertensive patients respond to sodium loading with either a blunted sympathetic deactivation3 or an impaired cardiac parasympathetic activation,4, 5 limited evidence of an altered autonomic cardiovascular modulation is available in normotensive subjects.…”