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.

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The effect of the state of sodium balance on the activity of the sympathetic nervous system has been evaluated previously by measuring urinary catecholamine excretion. Since urinary catecholamine may be affected by factors such as renal function or renal production of catecholamines, blood catecholamines may provide a better index of the activity of the sympathetic nervous system. The present study was undertaken to evaluate the effect of varying sodium intake on blood catecholamines.Thirteen normal subjects were studied for a period of 3 weeks in a metabolic ward. They received during the first, second, and third week 10, 100, and 200 meq sodium/day, respectively. On the seventh day of each week, when the patients had achieved sodium balance, urinary sodium excretion as well as blood levels of PRA, norepinephrine (NE), epinephrine (Ep), and dopamine (D) were measured in the supine position, at 5, 10, 15, and 20 min of upright posture, and at the end of 40 min of ambulation.The results show that: 1) blood levels of NE, Ep, and D as well as PRA were significantly higher during low sodium intake than during medium or high sodium intake, 2) as in the case of PRA, there was an inverse relationship between the blood levels of NE, Ep, and urinary sodium excretion; 3) upright posture produced a significant increment in the blood levels of NE which was not affected by sodium intake; and 4) the increment in PRA with posture was significantly greater during low sodium intake than with medium high sodium intake.The data demonstrate that: 1) the plasma levels of NE, Ep, and D are affected by the state of sodium balance, particularly during marked sodium depletion; and 2) meaningful interpretation of the significance of the blood levels of catecholamines should be made with reference to indices of sodium balance, such as urinary sodium excretion. (JClin Endocrinol Metab 48: 26, 1978) S EVERAL lines of evidence point toward the possible role of increased activity of the sympathetic nervous system in the genesis of essential hypertension (1-3). Esler et al. found hemodynamic evidence of sympathetic hyperactivity in a group of patients with high renin hypertension (4). However, Mitchell et al. (5) did not find differences in plasma catecholamine levels among hypertensive patients with different levels of PRA. The data on the relationship between urinary or blood catecholamines and essential hypertension are controversial. Some investigators have reported elevated levels of urinary catecholamines in 5-33% of patients (6-9), whereas others have found decreased excretion (10). Measurements of blood levels of catecholamines did not reveal a

Plasma catecholamines, hand-grip exercise and orthostatic stress were used to assess sympathetic nerve function in 14 hypertensive patients with mild to moderate renal failure and, for comparison, in 14 age-matched normal subjects. Furthermore, acute and chronic administrations of clonidine were used to determine a participation of the sympathetic nervous system in the maintenance of hypertension in these patients. Baseline mean blood pressure (MBP), plasma norepinephrine (NE), plasma renin activity (PRA) and aldosterone were elevated in patients with renal failure. During hand-grip exercise, the rise in MBP and in heart rate was blunted in these patients. During orthostasis, MBP decreased more while the increments in NE were greater in hypertensive patients that in normal subjects. Acute administration of clonidine (200 µg orally) resulted in a significant decrease in MBP, heart rate, NE, PRA, and aldosterone. There was a significant (p < 0.01) correlation between the decrease in NE and the fall in MBP. After 6 weeks of treatment, clonidine produced a significant decrease in MBP, heart rate, NE and aldosterone, but not in PRA. Chronic treatment with clonidine produced a slight but significant (p < 0.05) rise in serum potassium and in serum creatinine. Exchangeable sodium and plasma volume did not change significantly. The data indicate that abnormalities in the function of the sympathetic nervous system are already evident in patients with mild to moderate renal failure. The data also suggest that the sympathetic nervous system may participate in the maintenance of the hypertension in these patients.