Sodium Sensitivity Research Articles

Sodium sensitivity in young adults with high resting end-tidal CO2.

Previous research with normotensive adults aged over 40 years ('older') found that sensitivity of blood pressure of subjects with high resting end-tidal partial pressures of CO2 to high sodium intake was greater than normal. To test the hypothesis that the lesser sensitivity of blood pressure of young normotensive adults to high sodium intake is also a function of resting end-tidal partial pressure of CO2. Forty-eight Caucasian men and women (age 28.5 +/- 1.4 years) had a lower than normal dietary intake of sodium chloride for 4 days, and then ingested sodium chloride capsules for 7 days (an additional 190 mmol/day sodium chloride). Resting end-tidal partial pressure of CO2 and blood pressure, and 24 h ambulatory blood pressure, were measured before and after the high-sodium diet. Overnight urine samples were collected before and after the high-sodium diet to determine dietary compliance, and to assess changes in urinary excretion of endogenous digitalis-like factors (a ouabain-like factor, and a marinobufagenin-like factor) that covary with plasma volume. Subjects with high end-tidal partial pressures of CO2 had lower resting heart rates and lower urinary excretion of ouabain-like factor before sodium loading. Sodium loading decreased mean partial pressure of CO2 (by 0.8 +/- 0.2 mmHg) and increased only ambulatory systolic blood pressure (by 2.1 +/- 0.8 mmHg) for the whole group. However, the changes in resting systolic (r = 0.32, P < 0.025) and diastolic (r = 0.36, P < 0.01) blood pressures and in 24 h systolic (r = 0.28, P < 0.05) blood pressure after sodium loading were all positive functions of individual resting end-tidal partial pressures of CO2. Sodium loading increased urinary excretion of marinobufagenin-like factor (by 1.78 +/- 0.88 nmol) and the magnitude of the individual increase was a function of end-tidal partial pressure of CO2. The results indicate that a high resting partial pressure of CO2 augments the effects of high sodium intake on plasma volume, levels of endogenous digitalis-like factors, and blood pressure in young normotensive humans.

Stress and salt intake: experimental data on Dahl salt­resistant and salt­sensitive rats

The objective of the study was to evaluate the susceptibility of genetically predisposed to salt sensitivity Dahl rats to psychological stress and the effect of sodium ion on stress development. After weaning, Dahl salt-resistant (DR) and two groups of salt-sensitive (DS) rats were fed low-Na (0.5 per cent NaCI) and high-Na (8 per cent NaCI) diets for 2 months. A constellation of sensorimotor and behavioural tests were employed. The psychological stress was produced using a new model of acoustic startle device. DS weanling rats showed significantly increased sensorimotor reactivity, increased emotionality and increased sensitivity to acoustic stress, as compared to DR weanling rats. All the above parameters were exaggerated after 2-month Na loading: there was a significant decrease in the latency of the stressful response and increased magnitude of the hypertensive response to auditory stress. Blood pressure of Na-loaded DS rats increased by 43 per cent after auditory stress, as compared to 18 per cent increase in the Na-restricted rats. The effect of Na ion was mediated by an increased activity of the sympathetic nervous system (SNS). The chronic effect of Na restriction showed reduced SNS responsiveness and diminished neurohumoral reserve to maintain cardiovascular homeostasis. Risks of both Na loading and Na depletion in sodium sensitivity were discussed.

Insulin sensitivity is associated with blood pressure response to sodium in older hypertensives.

The purpose of this study was to determine whether sodium-resistant hypertensives are more insulin resistant and whether dietary sodium restriction improves insulin sensitivity in older hypertensives. Insulin sensitivity was assessed by a frequently sampled intravenous glucose tolerance test to determine the insulin sensitivity index (SI) after 1 wk each of low- (20 mmol.l-1.day-1) and high- (200 mmol.l-1.day-1) sodium diets in 21 older (63 +/- 2 yr) hypertensives. Subjects were grouped on the difference in mean arterial blood pressure (MABP) between diets [sodium sensitive (SS): > or = 5-mmHg increase in MABP on the high-sodium diet (n = 14); sodium resistant (SR): < 5-mmHg increase in MABP on the high-sodium diet (n = 7)]. There was no dietary sodium effect on fasting plasma insulin or SI. An analysis of variance indicated a significant (P = 0.0002) group effect, with SS individuals having lower fasting plasma insulins on the low- (13 +/- 2 vs. 27 +/- 3 microU/ml) and high- (12 +/- 2 vs. 22 +/- 3 microU/ml) sodium diets compared with SR individuals. Similarly, there was a significant (P = 0.0002) group effect in regard to SI, with SS individuals having significantly higher SI on the low- (3.26 +/- 0.60 vs. 0.91 +/- 0.31 microU x 10(-4).min-1.ml-1) and high- (3.45 +/- 0.51 vs. 1.01 +/- 0.30 microU x 10(-4).min-1.ml-1) sodium diets compared with SR individuals. We conclude that SR individuals exhibit a greater degree of insulin resistance than SS individuals and that dietary sodium restriction fails to improve insulin sensitivity regardless of sodium sensitivity status.

Pharmacogenomics: a new approach to individual therapy of hypertension?

The individual variation in the efficacy of and tolerability to antihypertensive drugs in human essential hypertension is linked to the genetic heterogeneity of this multifactorial disease. Different approaches have been pursued in the attempt to correlate a specific responsiveness to the therapy with some phenotypic traits of the patients, such as the renin-angiotensin profile or the characteristics of cell ion transports. More recently, a genetic approach to the study of the mechanisms underlying hypertension has led to the identification of some quantitative trait loci or genes that influence blood pressure in both animal models and patients. Also, individual variation to therapy can now be studied from the genetic point of view using pharmacogenomics, that is, the study of the genes or loci which are involved in determining the responsiveness to a given drug. Only a few examples of this approach are available to date. Our group has identified a polymorphism of the genes for the cytoskeletal protein, adducin, which is linked to both rat and human hypertension, sodium sensitivity and to the pressor responsiveness to diuretic therapy. These results, together with the indication that adducin can play a functional role by modulating the cellular sodium transport, have led to the identification of a new antihypertensive compound, which could be a candidate for the selective treatment of those patients in whom alterations of the renal sodium handling are associated with specific genetic traits such as the polymorphism for adducin.

Sodium sensitivity and cardiovascular events in patients with essential hypertension

In patients with sodium-sensitive hypertension, glomerular pressure is increased and microalbuminuria, a marker of glomerular hypertension, is a predictor of cardiovascular events. Similarly, the lack of a nocturnal decrease in blood pressure in these patients is also associated with an increased risk of cardiovascular events. We hypothesised that sodium sensitivity may be the common factor and carried out a retrospective study of cardiovascular events in patients with essential hypertension who had had sodium sensitivity measured in our clinic. Sodium sensitivity was assessed in about 350 patients with essential hypertension during the initial investigation of their disorder. The definition of sodium sensitivity was a 10% or greater difference in blood pressure on low-sodium or high-sodium diets. By alphabetical order, the records of 201 patients were obtained and 156 patients without pre-existing disorders were followed up. The records of patients who had a cardiovascular event or died were reviewed without knowledge of the patient's sodium-sensitivity status. 62 patients were deemed sodium sensitive and 94 non-sodium sensitive. Left-ventricular hypertrophy was found more frequently in the sodium-sensitive group than in the non-sodium-sensitive group (38 vs 16%; p < 0.01), whereas significantly fewer patients in this group smoked (23 vs 42%; p < 0.05). There were 17 cardiovascular events in the sodium-sensitive group and 14 in the non-sodium-sensitive group. The rate of total, non-fatal and fatal cardiovascular events, was 2.0 per 100 patient-years in the non-sodium-sensitive group and 4.3 per 100 patient-years in the sodium-sensitive group. Cox's proportional-hazards model identified sodium sensitivity (p < 0.01), mean arterial pressure (p < 0.01), and smoking (p < 0.01) as independent cardiovascular risk factors. Cardiovascular events occurred more frequently in patients with sodium-sensitive hypertension. Sodium sensitivity is an independent cardiovascular risk factor in Japanese patients with essential hypertension.

Sodium, blood pressure, and arterial distensibility in insulin-dependent diabetes mellitus.

We investigated 24-hour ambulatory blood pressure and arterial distensibility, a marker of biophysical vessel wall properties, in 32 normoalbuminuric type I diabetic patients and 32 healthy control subjects on diets containing 50 mmol and 200 mmol sodium per day. The increase in daytime diastolic blood pressure from 50 to 200 mmol sodium was significantly higher in the diabetic patients than in the control subjects (2.3+/-4.9 versus 0.2+/-3.7 mm Hg, P<.05). On a high sodium regimen, femoral artery distensibility was decreased in the diabetic patients compared with the control subjects (19.2+/-7.6 versus 24.1+/-9.3 10[-3]/kPa, P<.05). Angiotensin-converting enzyme inhibition in the diabetic patients on a high sodium diet decreased daytime diastolic blood pressure and increased femoral artery distensibility. The blood pressure decrease in response to angiotensin-converting enzyme inhibition correlated significantly with the blood pressure increase to sodium (for 24-hour systolic and diastolic blood pressure, r=.72, P<.001 and r=.76, P<.001). In addition, we found that in the diabetic patients on a high sodium diet, the renal blood flow response to exogenous angiotensin II was not bimodally distributed, as is the case in essential hypertension, in which a subgroup of the patients are characterized by sodium sensitivity of the blood pressure and an abnormal renal blood flow response to exogenous angiotensin II ("nonmodulator phenotype"). These results show that blood pressure in insulindependent diabetes mellitus is sodium sensitive, but that this is not related to the nonmodulator phenotype, and suggest that in IDDM a relatively high sodium intake may be a factor that predisposes to the development of diabetic vascular disease.

Sensitivity of blood pressure and renin activation during sodium restriction.

The objective of the present study was to explore the interrelationships among cumulative sodium loss, renin activation, and blood pressure changes during sodium restriction in essential hypertensive patients. Specifically, we wanted to know whether the degree of sodium sensitivity of blood pressure depends on renin activation during steady state or on initial renin activation during the first days of sodium restriction. Sixty-seven untreated essential hypertensive patients were admitted to a metabolic ward for 8 days and put on a sodium restricted diet of 55 mmol/d from the second to the last day. Urinary excretions of sodium, potassium, and creatinine were determined along with mean arterial pressure and weight during 7 days. Besides measurements in steady state condition (after 7 days), active plasma renin concentration, aldosterone, and catecholamines were also assessed during the first 3 days of sodium restriction. Analyzable data are available for 55 patients. Baseline sodium excretion and the activation of renin during the first 3 days both appeared to be predictors of total sodium loss after 7 days. Changes in blood pressure were not related to changes in sodium balance, but they were to baseline blood pressure, baseline norepinephrine, and renin activation during the early phase of sodium restriction. In addition, blood pressure appeared to fall more when the normal relationship between sodium loss and early (but not late) activation of renin was disturbed. We conclude that sodium sensitivity of blood pressure during sodium restriction is associated with a relative unresponsiveness of the renin system during the early phase of sodium loss rather than to absolute renin levels during steady state.

Implications of the linear pressure-natriuresis relationship and importance of sodium sensitivity in hypertension.

Although the concept of the pressure-natriuresis curve is very clear, considerable confusion concerning its importance and utility in understanding the pathophysiology of hypertension persists. We recently showed that the pressure-natriuresis curve could be considered linear. In this brief review, we would like to stress the advantages of treating it as a line. Its linear approximation simplifies understanding of the sodium sensitivity of the blood pressure and mechanisms of hypertension. The blood pressure can be expressed as the sum of two components: the non-sodium-sensitive component determined by the x intercept of the pressure-natriuresis curve and the sodium sensitive one determined by the product of the reciprocal of the slope and the amount of sodium intake. Theoretically, it can be affected in two different ways to cause hypertension; either a parallel shift along the blood pressure axis toward a higher blood pressure level due to the increase in the x intercept or a decrease in the slope. The parallel shift induces non-sodium-sensitive hypertension, whereas the decrease in slope induces sodium-sensitive hypertension. Thus, the linear approximation makes the definition of the sodium sensitivity of the blood pressure very clear and, furthermore, suggests that mechanisms of hypertension can be clarified if the determinants of the x intercept and the slope of the pressure-natriuresis curve are known. A clear definition of sodium sensitivity allows us to study its importance as a marker of a greater risk of renal and cardiovascular complications.

Sodium restriction shifts circadian rhythm of blood pressure from nondipper to dipper in essential hypertension.

Sodium restriction has been widely used for treatment of hypertension and renal diseases. Whether sodium restriction can transform the circadian rhythm of blood pressure from nondipper to dipper is examined. Patients (n=42) with essential hypertension were maintained on a high-sodium diet (12 to 15 g of NaCl per day) and a low-sodium diet (1 to 3 g/d) for 1 week each. On the last day of each diet, blood pressures were measured noninvasively every hour for 24 hours with an automatic oscillometric device. Twenty-one patients were classified as non-sodium sensitive whereas 21 were classified as sodium sensitive on the basis of a > or = 10% change in 24-hour mean arterial pressure caused by sodium restriction. Nocturnal blood pressure fall was significant in the non-sodium sensitive subjects but not in sodium-sensitive subjects. There was a significant interaction between sodium restriction and nocturnal fall in blood pressure only in the sodium-sensitive subjects, indicating that the degree of the nocturnal fall was affected by sodium restriction. Furthermore, changes in the nocturnal fall induced by sodium restriction had a positive relationship with sodium sensitivity (r=.38, P<.02) and a negative relationship with the nocturnal fall before sodium restriction (r=-.75, P<.0001). These findings show the difference in nocturnal fall in blood pressure between the non-sodium sensitive and sodium-sensitive types of essential hypertension. The diminished nocturnal fall, recognized in the sodium-sensitive type, is restored by sodium restriction, indicating that the circadian rhythm of blood pressure shifted from a nondipper to a dipper pattern. On the other hand, the nocturnal fall is not affected by sodium restriction in the non-sodium sensitive type, and the circadian rhythm remains of the dipper variety.

Sexual dimorphism of sodium-sensitive renal-wrap hypertension.

One-kidney, figure-8 renal wrap or sham operation was performed on male and female rats to determine if a difference existed in the expression of hypertension between the sexes. Animals were prepared with radiotelemetry transmitters to monitor mean arterial pressure and heart rate continuously throughout an 8-week study. Dietary sodium content was changed during the post-renal-wrap period from normal (100 micromol/g chow) to high (2000 micromol/g chow) to low (<2 micromol/g chow) to assess sodium sensitivity. Both male and female rats experienced an increase in arterial pressure after the renal-wrap procedure; however, the hypertension was significantly attenuated in the females. High salt caused a further increase in both groups of rats that was again attenuated in the female rats. Low sodium diet reduced arterial pressure in all groups of rats. Heart rate was significantly elevated in the female rats during all dietary interventions. The data were fit to a cosine function to analyze circadian rhythm changes. An increase in the light/dark difference for arterial pressure in the hypertensive rats during high salt diet resulted in an increase in the circadian amplitude (range of the rhythm). In the normotensive rats fed a high salt diet, the arterial pressure acrophase (peak of rhythm) was delayed while the heart rate acrophase was shifted to an earlier time. These studies showed that female rats are protected against one-kidney, figure-8 renal-wrap hypertension and are less sensitive to the effects of sodium.

Change in blood pressure during altered sodium intake is not associated with calciotropic hormone level.

1. We evaluated the effects of the dietary restriction of sodium chloride on blood pressure and systemic calcium metabolism in 19 in-patients with essential hypertension (11 men and 8 women, mean age 49.9 +/- 12.1 years). 2. All patients received a high-sodium diet (250 mmol/day) for 1 week, followed by a low-sodium diet (10 mmol/day) for another week. Intake of potassium (100 mmol/day) and of calcium (15 mmol/day) were kept constant throughout the study. 3. Sodium restriction significantly reduced the mean blood pressure (from 114.0 +/- 1.9 to 105.0 +/- 13.7 mmHg, P < 0.01). Urinary calcium excretion was significantly reduced (from 5.1 +/- 2.4 to 2.2 +/- 1.0 mmol/day, P < 0.01). 4. The change in mean blood pressure after sodium restriction was not correlated with a change in any parameter of calcium metabolism [whole blood ionized calcium, plasma intact parathyroid hormone, or 1,25-(OH)2 vitamin D3]. 5. Plasma renin activity during a regular sodium diet, an index of renin status, was significantly and inversely correlated with the change in blood pressure during sodium restriction, but not with any change in the parameters of calcium metabolism. 6. We conclude that sodium restriction reduces blood pressure and decreases urinary calcium excretion. However, we observed no significant role of extracellular calcium concentration or of calciotropic hormone concentration in the mechanism of sodium sensitivity.

80. Sodium sensitivity of blood pressure during sodium restriction is related to inadequate activation of renin during the early phase of sodium loss

80. Sodium sensitivity of blood pressure during sodium restriction is related to inadequate activation of renin during the early phase of sodium loss

Role of nitric oxide in the arterial pressure and renal adaptations to long-term changes in sodium intake.

The goals of this study were to determine whether long-term nitric oxide (NO) synthesis inhibition in dogs results in an increase in the sodium sensitivity of arterial pressure and whether changes in plasma renin activity or the plasma concentrations of arginine vasopressin (AVP) and aldosterone play an important role in this hypertension. Studies were conducted in a control group and groups that received NO inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) at 10 or 25 microg x kg(-1) x min(-1). Each group was challenged with normal, low, and high sodium intake for periods of 5 days each. Urinary nitrate + nitrite excretion (UNOx) more than doubled in the control group during high sodium intake. In both L-NAME groups, UNOx decreased significantly, there was a hypertensive shift in the relation between urinary sodium excretion and arterial pressure, and urinary sodium excretion remained normal even in the high-sodium intake period. L-NAME infusion did not change the sodium sensitivity of arterial pressure or plasma renin activity, plasma aldosterone, and plasma AVP. In conclusion, the data suggest that, in dogs, increases in NO synthesis are not necessary to excrete a chronic sodium load, and decreases in NO do not increase the sodium sensitivity of arterial pressure.

Pathophysiology of sodium sensitivity and resistance: From humans to rats—Mechanisms and implications

Pathophysiology of sodium sensitivity and resistance: From humans to rats—Mechanisms and implications

The possible role of protein phosphatase 2A in the sodium sensitivity of the receptor binding of opiate antagonists naloxone and naltrindole.

In striatal membrane preparation used for receptor binding experiments high levels of protein phosphatase 1 and 2A activities were detected using [32P]phosphorylase a as substrate. Sodium chloride decreased the activity of protein phosphatase 2A and increased the activity of protein phosphatase 1 in a concentration-dependent manner. Sodium chloride facilitated the saturation binding of naloxone and naltrindole in rat striatal membrane preparation preincubated with ATP (50 microM) and MgCl2 (5 mM). Preincubation with calyculin A (1 nM) further increased the binding of naloxone. Addition of okadaic acid in a concentration of 2 nM, which is specific for the inhibition of protein phosphatase 2A, augmented the number of binding sites of naloxone or naltrindole. The results suggest a protein phosphatase-dependent regulation of the binding of opiate ligands in the striatum.

Novel regulation of peripheral gustatory function by the immune system.

Soon after adult rats receive unilateral chorda tympani nerve section in combination with dietary sodium restriction, neural taste responses recorded from the intact, contralateral chorda tympani nerve are substantially reduced. We hypothesized that the immune system is compromised in sodium-restricted rats, which leads to functional alterations in the peripheral taste system after neural injury. Here, immune function was stimulated with a systemic injection of lipopolysaccharide (LPS), and neurophysiological responses were recorded from the uncut chorda tympani 4-10 days after nerve section to determine if normal sodium sensitivity was restored. Rats receiving nerve section, dietary sodium restriction, and LPS exhibited normal sodium responses. In intact rats, injection of LPS alone or LPS injection combined with sodium restriction had no effect on taste responses to sodium stimuli. Surprisingly, combining nerve section, LPS injection, and maintenance of rats on a normal diet induced supersensitive responses to sodium. These findings are the first to demonstrate that the immune system can regulate peripheral gustatory function.

Arterial alterations in hypertension with a disproportionate increase in systolic over diastolic blood pressure.

Although systolic and diastolic blood pressure and cardiovascular risk are directly related in epidemiologic studies, the results of large therapeutic trials in mild to moderate hypertension have indicated that the prevention of cerebrovascular accidents was much more effective than that of coronary ischemic accidents. Actually, a significant decrease in coronary events was observed only in aged populations in which systolic (and not diastolic) blood pressure was chosen as criterion of entry. Whether the choice of the mechanical factor (systolic or diastolic blood pressure or both) used to define hypertension might have created a bias in the studied populations remains an important question. Above 50 years of age, most hypertensive populations are characterized by a disproportionate increase in systolic over diastolic blood pressure, so that the pulsatile component of blood pressure is strikingly augmented. This pattern is commonly observed in old people with essential hypertension, in hypertensive subjects with advanced renal failure undergoing hemodialysis and in atherosclerotic subjects with hypertension, particularly those with atherosclerosis of the lower limbs and cerebral vessels. In all these populations, the disturbed pulse pressure is associated with significant alterations in large conduit arteries involving hypertrophy of central and peripheral large vessels and increased values of operational stiffness and altered wave reflections which return during the systolic (and not the diastolic) component of the aortic blood pressure curve. Sodium sensitivity is commonly observed in these patients, so that low doses of diuretics correct the increased pulse pressure, particularly in those with normal or low plasma renin activity. Although strong interactions may be observed between the pulsatile component of blood pressure and the arterial changes in hypertension, much more research is required before a clear-cut cause-effect relationship can be established between these two variables. With the exception of diuretic therapy in the elderly, there are at present no treatments that can selectively reduce pulse pressure or reverse the arterial changes or both in patients with essential hypertension and a disproportionate increase in systolic blood pressure.

Renal function reserve and sodium sensitivity in essential hypertension

It has been postulated that glomerular capillary pressure is elevated in sodium-sensitive types of hypertension. In addition, the presence or absence of renal function reserve, in response to a chronic protein load, is thought to be useful in predicting the existence of glomerular hypertension. Intrarenal hemodynamic parameters in the sodium-sensitive type of essential hypertension were therefore calculated by analyzing the pressure-natriuresis curve, and the preservation of renal function reserve was evaluated. Fifteen patients with essential hypertension were maintained on a normal sodium diet for 1 week and a low-sodium diet for a second week in study 1. This protocol was repeated for low and high protein intake in 8 patients in study 2. Subjects in study 1 whose mean arterial pressure was reduced by more than 10% by sodium restriction were considered sodium sensitive (n = 7), with the remaining patients classified as non-sodium sensitive (n = 8). There were no significant differences in mean arterial pressure (125 ± 2 mm Hg), glomerular filtration rate (80 ± 3 ml/min), or renal plasma flow rate (355 ± 24 ml/min) on the normal sodium diet between sodium-sensitive and non-sodium-sensitive patients. Glomerular capillary pressure (59 ± 2 mm Hg vs 47 ± 1 mm Hg, p < 0.0002) was estimated to be elevated in sodium-sensitive patients relative to that in non-sodium-sensitive patients, whereas the whole kidney ultrafiltration coefficient of glomerular capillary walls (0.068 ± 0.009 (ml/sec)/mm Hg vs 0.221 ± 0.042 (ml/sec)/mm Hg, p < 0.005) was decreased. Chronic protein loading increased both glomerular filtration and renal plasma flow rates in study 2. Although the sodium sensitivity of blood pressure showed no significant correlation with the increase in either glomerular filtration or renal plasma flow rate, it showed a weak negative correlation with the increase in filtration fraction (r = -0.69, p < 0.06), which is the ratio of the two rates. Taken together, these results suggest that glomerular capillary pressure is elevated and renal function reserve is impaired in patients with sodium-sensitive essential hypertension.

Component characteristics of the vectorial transport system for taurine in isolated bovine retinal pigment epithelium.

1. A wide range of substrate concentrations (5-1600 microM) were used to screen for the presence of systems capable of transporting taurine into isolated and free-floating samples of bovine retinal pigment epithelium (RPE). Both high and low affinity systems displaying Michaelis-Menten saturation kinetics were identified. The high affinity system was characterized by a K(m) of 23 microM and a V(max) of 86.7 pmol (5 min)(-1) (4 mm disc of tissue sample)(-1). Similarly, the low affinity system was characterized by a K(m) of 507 microM and a V(max) of 344 pmol (5 min)(-1)(4 mm disc)(-1). 2. Ussing-type incubation chambers and double-label radiotracer techniques were used to assess the presence of specific taurine carriers on apical and basolateral surfaces of the RPE. High affinity carriers were shown to be present on both surfaces and the kinetic constants (K(m) and V(max)) for apical and basolateral systems were determined as 23.2 microM and 34.8 pmol (5 min)(-1) (4 mm disc)(-1) and 29 microM and 54.7 pmol (5 min)(-1)(4 mm disc)(-1), respectively. Both these high affinity systems were sodium dependent with a Hill coefficient of about 2.0 indicating that two sodium ions are required for the translocation of one molecule of taurine. The low affinity system was unevenly distributed over the two surfaces of the RPE, basolateral capacities being roughly twofold higher. The basolateral system was totally insensitive to sodium whereas the apical one with 50% sodium sensitivity suggested the presence of low affinity carrier heterogeneity. 3. A temperature-dependent mechanism for the release of pre-loaded taurine from bovine RPF was also demonstrated. 4. The effect of [K+]o trans-RPF gradients on the vectorial transport of taurine across the isolated preparation was also investigated. The results demonstrated that the direction and magnitude of taurine transport could be controlled by physiological variations in the extracellular concentration of potassium. 5. The determined kinetic parameters of the carriers were used to construct a working model of the vectorial pathway for the translocation of taurine across bovine RPE. This estimated the level of free intracellular taurine to be in the micromolar range. However, direct measurements of total RPE taurine by high performance liquid chromatography showed levels of 19.5 +/- 3.6 mM indicating that the major taurine pool in bovine RPE exists in the bound form. The model also showed that the magnitude and direction of net transport was a function of the transepithelial taurine gradient.

Modulation of target tissue response to angiotensin II and sodium sensitivity in Japanese patients with essential hypertension.

"Non-modulators" are essential hypertensive patients who fail to modulate an adrenal response, renovascular response, or both, to angiotensin II (Ang II). The aim of the present study was to characterize "non-modulators" among Japanese patients with normal-renin essential hypertension and to determine whether non-modulation is related to sodium sensitivity of blood pressure. The increase in plasma aldosterone concentration (PAC response) and the decrease in renal plasma flow (RPF response) in response to Ang II infusion (3 ng/kg/min) were assessed in 15 Japanese patients with essential hypertension who received a high sodium diet (250 mEq/d) followed by a low sodium diet (10 mEq/d). The subjects were divided into two groups (6 modulators and 9 non-modulators) based on their ability to modulate the PAC response during sodium restriction. There was no significant difference between modulators and non-modulators in electrolyte balance or in plasma Ang II levels on either diet. Changes in the PAC response during sodium restriction were significantly correlated with the change in mean blood pressure during sodium restriction (r = -0.67, p < 0.01), while changes in the RPF response were not. RPF responses in both groups decreased during sodium restriction, although an effect on the RPF response in non-modulators was unexpected. These results suggest that non-modulators do exist among Japanese patients, but that this defect does not involve both the adrenal gland and the kidney. Apparently, only non-modulation of the adrenal response is involved in the mechanism of sodium sensitivity.