Salt-resistant Patients Research Articles

Pressor reactivity to norepinephrine and angiotensin in salt-sensitive hypertensive patients.

The mechanisms responsible for increased blood pressure in response to a high dietary sodium intake in salt-sensitive patients with essential hypertension are only partially understood. The possibility that increased reactivity to pressor hormones might contribute to hypertension in these patients has not been adequately investigated. We studied 11 salt-sensitive and 15 salt-resistant patients with essential hypertension while they were ingesting a diet with 20 meq/day sodium for 9 days or one with 200 meq/day sodium for 14 days. During the last 4 days of each dietary regimen, they received 30 mg/day of slow-release nifedipine. Blood pressure response to increasing doses of norepinephrine and angiotensin II (Ang II) was studied at the end of each of four phases of the study. Salt-sensitive patients exhibited a greater blood pressure response to norepinephrine than salt-resistant patients, irrespective of the dietary sodium intake and whether we took into account the dose infused or the actual plasma levels of norepinephrine achieved during the infusion. The blood pressure response to Ang II, on the other hand, was greater in salt-sensitive than salt-resistant patients during low but not during high sodium intake. The blood levels of norepinephrine achieved during the infusion of this hormone were lower in salt-sensitive than in salt-resistant patients. These studies indicate that an increased reactivity to the pressor action of norepinephrine might contribute to the maintenance of hypertension in salt-sensitive patients. The increased reactivity appears to be specific for norepinephrine. In fact, we observed increased reactivity to Ang II during low but not during high sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet activity and salt sensitivity in the pathogenesis of systemic (essential) hypertension in black Africans.

Black essential hypertensive patients with a mean arterial pressure of 125 +/- 3 mm Hg (mean +/- SEM), and age and sex matched normotensive subjects with a mean arterial pressure of 89 +/- 2 mm Hg were studied under baseline conditions, after five days of salt restriction and after five days of salt loading. Salt sensitivity was defined as an increase of mean blood pressure exceeding 5% when progressing from low to high sodium intake. In vitro platelet responsiveness was assessed by aggregometry, and in vitro platelet activity by estimation of beta-thromboglobulin (BTG) in plasma and thromboxane B2 (TXB2) excretion rate. Salt sensitivity was present in 66% of hypertensive and 55% of the normotensive subjects. An increased platelet aggregability to ADP (25%), to epinephrine (34%) and to collagen (12%) was found in parallel with an increased in vivo platelet activity (BTG increased by 55% and TXB2 by 18%) in the hypertensives. All changes were significantly exaggerated in the salt sensitive as compared to salt resistant hypertensive patients.

Effect of dietary sodium intake on intracellular calcium in lymphocytes of salt-sensitive hypertensive patients.

High dietary Na+ raises mean arterial pressure (MAP) by more than 10% in salt-sensitive (SS) patients with essential hypertension. To test whether the rise in MAP in these patients is caused by a Na(+)-linked increase in [Ca2+]i in vascular smooth muscle cells, we measured [Ca2+]i in the lymphocytes of 14 patients with essential hypertension kept on a Na+ intake of 20 mEq/day for 9 days, and 200-mEq/day for 14 days. Nifedipine gastrointestinal transport system (GITS) (30 mg/day) was given during the last 4 days of each diet. We isolated lymphocytes on Ficoll-Hypaque gradient and measured [Ca2+]i levels using Fura-2 fluorescent dye. During low Na+ intake, there was no difference in MAP (102 +/- 3.5 v 93 +/- 3.8 mm Hg) and in lymphocytes [Ca2+]i (80 +/- 3.0 v 87 +/- 5.4 nmol/L) between the seven salt-sensitive and the seven salt-resistant patients. During high Na+ intake, MAP (92 +/- 2.8 mm Hg) and [Ca2+]i (85 +/- 6.8 nmol/L) did not change in salt-resistant patients. On the contrary, MAP (115 +/- 3.4 mm Hg) and [Ca2+]i (130 +/- 11.1 nmol/L) increased significantly (P less than .01) in the salt-sensitive patients. Nifedipine did not significantly alter MAP and [Ca2+]i in both groups of patients during low Na+ and in salt-resistant patients during high Na+ intake. On the contrary, during high Na+ intake, nifedipine decreased significantly (P less than .01) both MAP (104 +/- 2.4 mm Hg) and [Ca2+]i (89 +/- 5.7 nmol/L) in salt-sensitive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

High urinary dopa and low urinary dopamine-to-dopa ratio in salt-sensitive hypertension.

Dopamine in urine is derived substantially from renal uptake and decarboxylation of 3,4-dihydroxyphenylalanine (dopa), and increases in excretion of dopa normally parallel increases in excretion of dopamine during salt loading. Since patients with salt-sensitive hypertension may have decreased urinary excretion of dopamine during dietary salt loading, the present study was designed to evaluate the response of dopa to salt loading. Sixteen inpatients with normal-renin essential hypertension ate a constant metabolic diet containing 9 mmol/day sodium for 7 days, followed by the same diet but containing 249 mmol/day sodium for 7 days. Salt sensitivity was defined as an increase in mean arterial pressure of 8 mm Hg between the diets; on this basis, nine patients were salt-sensitive and seven, salt-resistant. The rate of urinary dopa excretion was significantly higher in the salt-sensitive patients throughout the study (mean rates 132 +/- 13 nmol/day in the salt-sensitive group and 78 +/- 9 nmol/day in the salt-resistant group for the 14 days of observation, p less than 0.01). When dietary sodium intake was increased to 249 mmol/day, urinary dopa excretion increased significantly more in salt-sensitive patients than salt-resistant patients. At the end of the high salt diet, dopamine excretion was significantly attenuated in the salt-sensitive patients, despite higher rates of dopa excretion. Thus, the urinary ratio of dopamine to dopa was decreased in salt-sensitive patients, regardless of salt intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Salt-induced plasticity in cardiopulmonary baroreceptor reflexes in salt-resistant hypertensive patients.

To investigate the effects of salt loading on cardiopulmonary and arterial baroreceptor reflexes, 34 hypertensive patients underwent two 4-day periods with different dietary sodium intakes (70 and 370 meq/day). The patients were classified as salt-sensitive or salt-resistant depending on whether the mean arterial pressure value obtained on day 4 of high salt intake did or did not increase by 8% or more. In 22 patients cardiopulmonary and carotid baroreceptor reflexes were assessed during each dietary period by measuring the reflex responses to the application of -10 mm Hg lower body negative pressure and of +60 mm Hg increase in neck tissue pressure. Salt-resistant patients (n = 16) retained less sodium than salt-sensitive patients (n = 6) and showed a reduction in plasma norepinephrine and forearm vascular resistance during high sodium intake, whereas the salt-sensitive patients did not. During low sodium diet, no significant differences could be detected in the reflex responses to cardiopulmonary and carotid baroreceptor unloading between the two groups. High salt diet, however, potentiated the gain of cardiopulmonary baroreceptor reflex, which was expressed as the increase in plasma norepinephrine or forearm vascular resistance per millimeter of mercury decrease in pulmonary capillary wedge pressure, only in the salt-resistant hypertensive patients. In addition, the atrial natriuretic factor response to changes in pulmonary capillary wedge pressure was significantly enhanced by high salt intake only in the salt-resistant hypertensive patients. The reflex responses to carotid baroreceptor unloading were unaffected by salt loading in either group. In the remaining 12 patients, the hemodynamic effects of graded lower body negative pressure (-5, -10, -15 mm Hg) and neck tissue positive pressure (+30, +45, +60 mm Hg) were tested for both diets. Again, high salt intake significantly potentiated the cardiopulmonary baroreceptor reflex gain, expressed as the slope of the linear correlation between the changes in forearm vascular resistance (mm Hg/ml/min/100 g) and pulmonary capillary wedge pressure (mm Hg), in salt-resistant (from 3.8 +/- 0.9 to 7.2 +/- 1.0, p less than 0.05) but not in salt-sensitive patients (from 4.2 +/- 0.9 to 3.2 +/- 0.6, NS). In conclusion, the present study demonstrates that high salt diet potentiates cardiopulmonary baroreceptor reflexes and enhances atrial natriuretic factor response in salt-resistant but not in salt-sensitive hypertensive patients. The salt-induced plasticity of cardiopulmonary baroreceptor reflexes may exert a protective effect against the development of salt-induced hypertension by augmenting the reflex vasodilatory response to volume expansion.(ABSTRACT TRUNCATED AT 400 WORDS)

Left Ventricular Hypertrophy Is More Marked in Salt-Sensitive Than in Salt-Resistant Hypertensive Patients

Besides the duration and severity of hypertension, several other factors have been shown to be related to left ventricular hypertrophy (LVH) in essential hypertension. The present study was conducted to examine the influence of salt sensitivity on LVH. Fifteen essential hypertensive ambulatory patients were submitted to a low-salt (30 mEq of Na/day for 7 days) and a high-salt (200 mEq of Na/day for 7 days) diet after 12 weeks on placebo. Daily urine collection was obtained during the whole study. After the placebo period, all patients were submitted to a complete clinical and laboratory investigation that included an echocardiogram (M-mode and two-dimensional). Five patients were salt-sensitive (mean blood pressure (BP) increase from the seventh day of the low- to the seventh day of the high-salt diet greater than 10%). No differences in weight, sex ratio, and duration of hypertension were obtained between salt-sensitive and -resistant patients. The initial BP was higher in the salt-sensitive patients. However, the difference was small and without statistical significance. The left ventricular weight was higher in the salt-sensitive than in salt-resistant patients (148 +/- 51 vs. 109 +/- 32 g/m2, p less than 0.05). The left ventricular end-diastolic diameter was also higher in the salt-sensitive patients (50 +/- 10 vs. 43 +/- 6 mm, p less than 0.05). The interventricular septum and posterior wall thicknesses were higher in salt-sensitive patients, although they did not reach statistical significance. In conclusion, salt-sensitive essential hypertensive patients are at a higher risk to develop LVH.

Salt sensitivity in human essential hypertension: effect of renin-angiotensin and sympathetic nervous system blockade.

We studied the acute effect of oral captopril (25mg) and clonidine(300 micrograms) on blood pressure (BP) in patients with essential hypertension successively maintained on a low (LSD) and high (HSD) salt diet. Seven patients were salt sensitive (SS) and seven were salt resistant (SR). The maximal decrease in diastolic BP caused by captopril in patients on the LSD was greater in SS than SR individuals. Baseline urinary norepinephrine levels did not change from LSD to HSD (p greater than 0.05) in SS patients and decreased in SR patients (p less than 0.05). The maximal decrease in mean BP during the clonidine test was the same for both diets (p greater than 0.05) in SS patients and was lower (p less than 0.05) for the HSD in SR patients. SS patients on the HSD presented a higher decrease in systolic BP than SR patients (p less than 0.05) during the clonidine test. These data suggest overactivity of the renin-angiotensin system in SS patients on the LSD and of the sympathetic nervous system in SS patients on the HSD and that the clonidine test could be a good indicator for identifying SS and SR patients.

Effects of calcium antagonists on deranged modulation of the renal function curve in salt-sensitive patients with essential hypertension

Two subsets of patients with essential hypertension have been identified based on their sensitivity to dietary sodium intake: the salt-sensitive and the salt-resistant patients. The renal function curve in salt-resistant patients is shifted to higher blood pressure levels but it remains parallel to that of normal subjects. On the contrary, the slope of the renal function curve in salt-sensitive patients is considerably depressed. It is postulated that this derangement may be related to an abnormal relation between sodium intake and sympathetic nervous system activity. It is also postulated that a link exists between abnormalities of sodium and calcium metabolism in hypertension and that reduced renin release, increased sympathetic activity and reduced renal sodium excretion in salt-sensitive patients may be related to a defect in sodium-linked cellular calcium transport. Calcium antagonists revert the derangements in the renal function curve and in renin release in salt-sensitive patients.

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

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.