High sodium diet and circulating digitalis-like compound in the rat

The effects of a high salt diet (8% NaCl) on blood pressure and intra-erythrocytic Na+ content were studied in Wistar rats. The ability of the plasma to inhibit the renal Na+,K+-ATPase activity and to cross-react with digoxin antibodies was also investigated. After 1 week, neither systolic blood pressure nor intra-erythrocytic Na+ content were modified, but plasma extracts slightly inhibited renal Na+,K+-ATPase (70.9 +/- 1.7 versus 76.3 +/- 2.1 mumol Pi/mg per h, P = 0.05). After 2 weeks, the plasma inhibitory activity, systolic blood pressure and intra-erythrocytic Na+ content were higher than corresponding values in control animals (65.5 +/- 1.6 versus 79.1 +/- 2.8 mol Pi/mg per h, P less than 0.001; 132 +/- 2 versus 114 +/- 4 mmHg, P less than 0.001, and 4.95 +/- 0.32 versus 3.81 +/- 0.36 mmol/l cells, P less than 0.05, respectively). After 3 months, the plasma digoxin-like immunoreactivity and its ability to inhibit the Na+ pump were elevated (68.7 +/- 7.9 versus 48.2 +/- 5.4 pg/ml, P less than 0.02; 57.8 +/- 1.8 versus 72.9 +/- 1.8 mumol Pi/mg per h, P less than 0.001, respectively) whereas intra-erythrocytic Na+ content had returned to control levels. The results demonstrated that this high salt intake led to simultaneous increases in systolic blood pressure and in the activity of a digitalis-like compound present in plasma. The inhibition of Na+,K+-ATPase was correlated with systolic blood pressure and digoxin-like immunoreactivity (r = 0.569, n = 76, P less than 0.001 and r = 0.414, n = 34, P less than 0.02, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nitric oxide production decreases after salt loading but is not related to blood pressure changes or nitric oxide-mediated vascular responses

BACKGROUND: Nitric oxide production is a homeostatic mechanism that may regulate blood pressure during salt loading. Salt-sensitive hypertension in animal models and in humans is characterized by increased blood pressure and decreased nitric oxide production after salt loading. It is not known if this impaired nitric oxide production is the result of hypertension or is a mechanism contributing to the blood pressure response to salt. METHODS AND RESULTS: The effects of salt loading on blood pressure, nitric oxide-mediated vasodilation and nitric oxide production were measured in 25 normotensive subjects after 6 days on either a high (400 mmol/day) or low (10 mmol/day) sodium, low nitrate diet. Mean arterial pressure increased during the high-salt diet [4 +/- 1 mmHg (mean +/- SEM)] in 12 subjects and remained unchanged or decreased (-4 +/- 1 mmHg) in 13 subjects. Plasma nitrite and nitrate, a measure of nitric oxide production, decreased significantly from 39 +/- 3.3 micromol/l during the low-salt diet to 22.4 +/- 2.4 micromol/l during the high-salt diet (P = 0.0001). However, changes in mean arterial pressure from low- to high-salt diet did not correlate with changes in plasma nitrite and nitrate (r = 0.14, P = 0.51). Forearm blood flow increased significantly (P <0.0001) in response to mental stress, a nitric oxide-mediated response, but was not affected by sodium intake (from 7.8 +/- 0.9 to 11.2 +/- 1.4 ml/min per 100 ml during low salt versus 8.5 +/- 1.2 to 10.4 +/- 1.3 ml/min per 100 ml during high salt,P = 0.3). CONCLUSIONS: Salt loading results in a decrease in nitric oxide production in both salt-sensitive and salt-resistant normotensive subjects, which is independent of changes in blood pressure and does not affect the nitric oxide-mediated vascular response to mental stress. In contrast to salt-resistant animal models, salt loading in healthy subjects does not increase nitric oxide production. Therefore, the increased blood pressure response to salt loading may occur through mechanisms other than nitric oxide, or salt-sensitive individuals are more sensitive to the reduced nitric oxide production that occurs after salt loading in both salt-sensitive and salt-resistant subjects.     

Uninephrectomy in young age or chronic salt loading causes salt-sensitive hypertension in adult rats

The importance of nephron endowment and salt intake for the development of hypertension is under debate. The present study was designed to investigate whether reduced nephron number, after completion of nephrogenesis, or chronic salt loading causes renal injury and salt-sensitive hypertension in adulthood. Rats were operated at 3 weeks of age (after completed nephrogenesis) and then subjected to either normal or high-salt diets for 6 to 8 weeks. Four different experimental groups were used: sham-operated animals raised with normal-salt diet (controls) or high-salt diet (HS) and uninephrectomized animals raised with normal-salt diet (UNX) or high-salt diet (UNX+HS). In the adult animals, renal and cardiovascular functions were evaluated and blood pressure recorded telemetrically under different sodium conditions (normal, high, and low). Hypertension was present in UNX+HS (122+/-9 mm Hg), UNX (101+/-3 mm Hg), and HS (96+/-1 mm Hg) groups on normal-salt diets compared with the controls (84+/-2 mm Hg), and the blood pressure was salt sensitive (high- versus normal-salt diet; 23+/-3, 9+/-2, 7+/-2, and 1+/-1 mm Hg, respectively). The hypertensive groups (UNX+HS, UNX, and HS) had increased diuresis and reduced ability to concentrate urine. The glomerular filtration rate (milliliters per minute) in anesthetized rats was reduced in the UNX+HS (2.36+/-0.30) and UNX animals (2.00+/-0.31) compared with both HS animals (3.55+/-0.45) and controls (3.01+/-0.35). Hypertensive groups displayed reduced plasma renin concentrations during high sodium conditions and hypertrophic kidneys and hearts with various degrees of histopathologic changes. In conclusion, at a young age after completed nephrogenesis, uninephrectomy or chronic salt loading causes renal and cardiovascular injury with salt-sensitive hypertension.     

Time-Related Alterations in an Endogenous Digitalis-Like Factor in the Development of Doca-Salt Hypertension in Rats

Time-related alterations in a digitalis-like factor in urine were examined by means of cross-reactivity with an anti-digoxin antibody during the development of hypertension in DOCA-salt rats. Daily urinary sodium excretion was also measured. After hypertension had developed, plasma levels of the digitalis-like factor were determined by two methods: radioimmunoassay for digoxin and a receptor binding assay using ³H-ouabain and a rat brain synaptosomal protein. Urinary digoxin-like immunoreactivity increased gradually and significantly in the DOCA-salt rats as compared with that of sham-operated high-salt rats and normal-salt rats. Urinary sodium excretion was significantly higher in the DOCA-salt rats, and a significant correlation (r = 0.56, p<0.001) was observed between the daily urinary digoxin-like immunoreactivity and daily sodium excretion. In plasma, both digoxin-like immunoreactivity and ouabain-like binding activity were significantly higher in the DOCA-salt rats than in the other 2 groups. These results suggest that digitalis-like factor plays an important role in the development of hypertension in DOCA-salt rats.     

Importance of the renin system for determining blood pressure fall with acute salt restriction in hypertensive and normotensive whites

Hypertensive (n=93) and normotensive (n=39) white individuals were given a high sodium intake of approximately 350 mmol/d for 5 days followed by a low sodium intake of 10 to 20 mmol/d for 5 days. With this acute and large reduction in salt intake, no significant change was seen in blood pressure in the normotensive individuals, but blood pressure decreased in the hypertensive individuals. Compared with normotensive subjects, hypertensive patients had a 7/7-mm Hg greater fall in blood pressure (P<0.05 for systolic and P<0.01 for diastolic, adjusted for age), with similar changes in urinary sodium excretion. From the high-salt to low-salt diet, plasma renin activity rose from 0.90 to 5.99 ng. mL(-1). h(-1) in normotensives, whereas in hypertensives it rose from 0.73 to only 3.14 ng. mL(-1). h(-1) (P<0.05 between hypertensives and normotensives). Plasma aldosterone rose by 1396 pmol/L in normotensive subjects and by 511 pmol/L in hypertensive patients (P<0.05). Significant inverse correlations were obtained for all subjects between the fall in blood pressure from the high-salt to low-salt diet and the rise in plasma renin activity and aldosterone that occurred in addition to the absolute level on the low-salt diet. These results demonstrate that the larger fall in blood pressure with an acute reduction in salt intake in hypertensives compared with normotensives is, at least in part, due to a less-responsive renin-angiotensin-aldosterone system in the hypertensive patients.     

Endogenous digoxin-immunoreactive substance in human pregnancies

We report the presence of an immunoreactive digoxin-like substance in blood from third trimester pregnant women. The sera from 51 women in the third trimester of pregnancy were analyzed by 4 commercially available digoxin RIAs. None of these patients was receiving digoxin. Digoxin immunoreactivity was detected in all patients by 3 of 4 assays. The measured values, in nanograms per ml digoxin equivalent, were (mean +/- SD): method A, 0.27 +/- 0.05; method B, 0.28 +/- 0.07; method C, 0.01 +/- 0.01; and method D, 0.15 +/- 0.06. Method B measured values greater than 0.50 ng/ml in sera from 5 patients. Digoxin immunoactivity was not detectable 24 h postpartum, suggesting a half-life in serum of 6 h or less. Exogenous digoxin added to these serum samples resulted in quantitatively additive increments above the endogenous measured levels. Three of 4 digoxin RIAs did not distinguish between true digoxin and the endogenous substance present in the sera of third-trimester pregnant patients. Preliminary evidence suggests that the endogenous digoxin immunoactivity is not due to elevation of levels of major known steroids in the blood of these women. Clinical management of women requiring digoxin therapy during pregnancy, therefore, is complicated by the inability to assume the same therapeutic range of digoxin in serum during the third trimester of pregnancy as in adult nonpregnant individuals.     

Acute elevations in salt intake and reduced renal mass hypertension compromise arteriolar dilation in rat cremaster muscle.

Alterations in arteriolar reactivity to dilator agonists were assessed in the skeletal muscle microcirculation of normotensive male Sprague-Dawley rats fed either high- (4% NaCl; HS) or low- (0. 4% NaCl; LS) salt diets and in reduced renal mass hypertensive rats (RRM-HT) on a high-salt diet for 3 days. An in situ cremaster muscle preparation was superfused with physiological salt solution, transilluminated, and viewed via television microscopy. A videomicrometer was used to measure changes in diameter of distal arterioles in response to increasing concentrations of acetylcholine (ACH), iloprost (ILO), cholera toxin (CT), forskolin (FOR), and sodium nitroprusside (SNP). Arteriolar dilation in response to ACH, ILO, and CT was significantly reduced in both HS and RRM-HT rats, while responses to FOR and SNP were decreased in RRM-HT rats only. The maximum dilation of the arterioles (determined during superfusion of the muscle with Ca2+-free solution containing 10(-4) M adenosine) was similar in the normotensive control animals on LS and HS diets, but was reduced in the RRM-HT rats, suggesting that early anatomic remodeling of the vessel wall may be occurring with RRM-HT. We conclude that arteriolar reactivity to endothelium-dependent and -independent vasodilator agonists is impaired as early as 3 days after the development of RRM hypertension or commencement of a high-salt diet in normotensive rats. Structural remodeling of the arteriolar wall, although becoming evident in the hypertensive rats, takes longer to develop than the impaired vasodilator reactivity.     

Salt loading affects cortisol metabolism in normotensive subjects: relationships with salt sensitivity

We studied cortisol metabolism together with insulin sensitivity [homeostatic model assessment (HOMA)] and renal hemodynamics in 19 salt-resistant (sr) and nine salt-sensitive (ss) normotensive subjects after a low- and high-salt diet. Results are described as high- vs. low-salt diet. Sum of urinary cortisol metabolite excretion (sum(metabolites)) increased in sr subjects (3.8 +/- 1.6 vs. 3.1 +/- 1.1 microg/min per square meter, P < 0.05) and decreased in ss subjects (2.3 +/- 1.0 vs. 2.9 +/- 1.1 microg/min per square meter, P < 0.05). Plasma 0830 h cortisol decreased in sr subjects but did not change significantly in ss subjects. In all subjects, the absolute blood pressure change correlated negatively with the percentage change in sum(metabolites) (P < 0.05) and positively with the percentage change in renal vascular resistance (P < 0.05). Sum(metabolites) during high-salt diet correlated negatively with the percentage changes in plasma 0830 h cortisol (P < 0.05) and renal vascular resistance (P = 0.05). HOMA did not change in either group, but the percentage change in HOMA correlated positively with the percentage change in plasma cortisol (P = 0.001) and negatively with the percentage change in sum(metabolites) (P < 0.01). Parameters of 11 beta-hydroxysteroid dehydrogenase activity were not different between groups and did not change. In conclusion, these data suggest that cortisol elimination is affected differently after salt loading in sr and ss subjects. Changes in circulating cortisol might contribute to individual sodium-induced alterations in insulin sensitivity.     

Digoxin-like immunoreactive substances in chronic liver disease

Digoxin-like immunoreactive substances, which cross-react with digoxin antibody, have been found to have natriuretic effect and Na+,K+-ATPase inhibitory effect. The role of digoxin-like immunoreactive substances in chronic liver disease was studied by radioimmunoassay in 63 serum and 60 urine samples from 58 patients with chronic liver disease and compared with 16 controls. Although the mean serum digoxin-like immunoreactive substances level of compensated chronic liver disease patients (0.06 +/- 0.05 ng per ml, p less than 0.01) was higher than that of controls (0.02 +/- 0.03 ng per ml), only four patients had serum digoxin-like immunoreactive substances higher than 0.10 ng per ml. Mean serum digoxin-like immunoreactive substances level was much higher in patients with decompensated chronic liver disease who had ascites (0.32 +/- 0.17 ng per ml, p less than 0.001), hepatorenal syndrome (0.57 +/- 0.20 ng per ml, p less than 0.001) and hepatic encephalopathy (0.43 +/- 0.20 ng per ml, p less than 0.001). Five patients with recent variceal hemorrhage requiring transfusions and saline infusion had significantly increased serum digoxin-like immunoreactive substances (mean: 0.16 +/- 0.06 ng per ml, p less than 0.001) before the development of clinically detectable ascites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet

The amount of sodium chloride in the diet of industrialized nations far exceeds physiological requirements. The impact of abundant dietary salt on skeletal health has yet to be established, but is potentially detrimental through increased urinary calcium losses. We examined the effect of increased dietary sodium chloride on urine calcium excretion and bone turnover markers in postmenopausal women and, further, whether potassium citrate attenuates the effects of increased dietary salt. Postmenopausal women (n = 60) were adapted to a low-salt (87 mmol/d sodium) diet for 3 wk, then randomized to a high-salt (225 mmol/d sodium) diet plus potassium citrate (90 mmol/d) or a high-salt diet plus placebo for 4 wk. Urine calcium, urine N-telopeptide, urine cAMP, serum osteocalcin, and fasting serum PTH were measured at the end of the low- and high-salt diets. On the high salt plus placebo diet, urine calcium increased 42 +/- 12 mg/d (mean +/- SEM), but decreased 8 +/- 14 mg/d in the high salt plus potassium citrate group (P = 0.008, potassium citrate vs. placebo, unpaired t test). N-telopeptide increased 6.4 +/- 1.4 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus placebo group and 2.0 +/- 1.7 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus potassium citrate group (P < 0.05, potassium citrate vs. placebo, unpaired t test). Osteocalcin, PTH, and cAMP were not significantly altered. The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone resorption marker caused by a high salt intake. Increased intake of dietary sources of potassium alkaline salts, namely fruit and vegetables, may be beneficial for postmenopausal women at risk for osteoporosis, particularly those consuming a diet generous in sodium chloride.     

Endogenous Inhibition of Red Blood Cell Na,K-ATPase in Essential and Pregnancy-Induced Hypertension

Digoxin-like inhibitors of Na, K-ATPase have been implicated in the pathophysiology of essential(EH) and pregnancy-induced hypertension(PIH). A technique that enhances dissociation of digoxin from red blood cells(RBC) was used to displace endogenous digoxin-like substances from RBCs. RBC membranes were preincubated in Na and ATP(Release) or Na, K, Mg and ATP (Retention) prior to measuring ATPase activity. Groups studied were: 39 men with EH and 34 controls plus 10 women with PIH and 17 normotensive controls. All displayed similar increases in Na, K-ATPase activity (24.0±7.9%) following Release. Plasma digoxin immunoreactivity(DI) was measured in pregnant women, m= 0.25±0.07 ng/ml. No DI was detected in nonpregnant women, but RBCs from these women demonstrated the same increase in Na, K-ATPase activity after Release. The 24% increase in activity achieved by Na and ATP preincubation can be reversed by adding K and Mg to the Release suspension. However, after RBC-bound digoxin is displaced by Release preincubation, addition of K and Mg cannot promote renewed binding and pump inhibition. Thus, the observed endogenous inhibition is not due to displacement of a digoxin-like substance but probably is related to alteration of the enzyme-membrane interaction. Furthermore, even though pregnant women demonstrate DI, an inhibitory susbstance with digoxin-like binding could not be recognized using theis technique.     

Observations on The “Cascade” of Na-K-ATPase Inhibitory and Digoxin - Like Immunoreactive Material in Human Urine: Possible Relevance To Essential Hypertension

Previous investigations have demonstrated an increased amount of a sodium pump inhibitor (N.H.) in plasma from humans with essential hypertension and from animals with various forms of experimental hypertension. The present study has employed Sephadex column and C₁₈reverse phase separation of urines from patients with essential hypertension and normal controls to distinguish “high”, “intermediate” and “low” molecular weight forms of N.H., measured through properties of Na-K-ATPase inhibition and digoxin-like immunoreactivity. The major difference between hypertensive and normotensive urines was a highly significant increase in the “intermediate” molecular weight form of N.H., as measured by Na-K-ATPase inhibition. In contrast, digoxin - like immunoreactivity was significantly decreased in urine from hypertensive patients. The results are compatible with an hypothesis that the defect in some forms of essential hypertension may be partial inhibition of enzymatic conversion of intermediate to final form of N.H., with the increased sodium pump inhibition primarily related to the precursor.     

Total digoxin-like immunoreactive factor(s) in healthy population, uncomplicated term pregnancies and neonates

Free digoxin-like immunoreactive factor(s) (DLIF) which may have a homeostatic role, as documented in different physiological conditions, but is generally undetectable in plasma from normal population. Total digoxin-like immunoreactive factor(s) (protein bound and free) can be estimated after plasma is heated. In this study, total digoxin-like immunoreactive factor(s) as measured in plasma in a well defined control population and compared to healthy term pregnant women and neonates, categories known to be associated with increased free digoxin-like immunoreactive factor(s) concentrations. The mean level of this factor(s) in the control group was 706 +/- 129 pg digoxin equivalent/ml (pg/ml) and was unaffected by age and sex. Significantly increased levels of total digoxin-like immunoreactive factor(s) were found in pregnant women and neonates (928 +/- 127 and 1242 +/- 367 pg/ml, respectively). We conclude that levels of total digoxin-like immunoreactive factor(s) are increased in term pregnancies and neonates, similarly to its free form. However total digoxin-like immunoreactive factor(s) is detected in the normal population as a plasma component, contrary to its free form, which is generally undetectable.     

Impaired cardiopulmonary baroreflex control of renal nerves in renal hypertension

We recently reported that arterial baroreflex control of renal nerve traffic is impaired in renal hypertensive rabbits. The purpose of this study was to determine if vagal cardiopulmonary baroreflex control of renal nerve traffic is also impaired. Experiments were performed in 10 hypertensive (mean arterial pressure +/- SE in conscious state, 110 +/- 3 mm Hg) and 10 normotensive (79 +/- 1 mm Hg) chloralose-anesthetized rabbits. Responses to graded blood volume expansion (+5, +10, +15 ml/kg) with dextran in saline were recorded with all baroreflexes intact, after sinoaortic baroreceptor denervation, and after vagotomy. With arterial and cardiopulmonary baroreflexes intact, volume expansion resulted in decreases in renal nerve traffic of -12 +/- 2%/mm Hg increase in left atrial pressure in normotensive rabbits, but of only -5 +/- 2%/mm Hg in the hypertensive rabbits (P less than 0.05). This difference is particularly striking in view of the larger maximum increases in arterial (25 +/- 7 vs. 12 +/- 3 mm Hg) and left atrial pressure (9 +/- 1 vs. 6 +/- 1 mm Hg) during volume expansion in hypertensive vs. normotensive rabbits. After sinoaortic baroreceptor denervation, the responses of normotensive rabbits were preserved (-11 +/- 3%/mm Hg), while those of hypertensive rabbits were impaired further (-2 +/- 1%/mm Hg). Vagotomy abolished responses of renal nerves to volume expansion in both groups. These data demonstrate striking impairment of vagal cardiopulmonary baroreflex control of renal nerve traffic in renal hypertension. Even though arterial baroreflexes have been shown to be abnormal in renal hypertension, they still may partially compensate for markedly impaired cardiopulmonary baroreflex control of the renal nerves.     

Salt loading on plasma asymmetrical dimethylarginine and the protective role of potassium supplement in normotensive salt-sensitive asians

Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. Because endothelial NO pathway is compromised in patients with salt-sensitive hypertension, we investigated whether the plasma ADMA can be modulated by chronic salt loading in normotensive salt-sensitive persons and its relationship with NO, and we further determined whether or not dietary potassium supplementation can reverse them. Sixty normotensive subjects (aged 20 to 60 years) were selected from a rural community of Northern China. All of the people were sequentially maintained on a low-salt diet for 7 days (3 g/day, NaCl), then a high-salt diet for 7 days (18 g/day), and high-salt diet with potassium supplementation for another 7 days (4.5 g/day, KCl). After salt loading, the plasma ADMA concentrations increased significantly in salt-sensitive subjects (0.89+/-0.02 micromol/L versus 0.51+/-0.02 micromol/L; P<0.05), whereas the plasma NOx levels reduced considerably (41.8+/-2.1 micromol/L versus 63.5+/-2.1 micromol/L; P<0.01). All of the abnormalities normalized when dietary potassium were supplemented (0.52+/-0.03 micromol/L versus 0.89+/-0.02 micromol/L for ADMA and 58.1+/-0.9 micromol/L versus 41.8+/-2.1 micromol/L for NOx). Statistically significant correlations were found among plasma ADMA level, the mean blood pressure, and the level of NO after salt loading in normotensive salt sensitive individuals. Our study indicates that high dietary potassium intake reduces blood pressure and ADMA levels while increasing NO bioactivity in normotensive salt-sensitive but not salt-resistant Asian subjects after salt loading.     

Insulin, renin-aldosterone system and blood pressure in obese people.

OBJECTIVE: To evaluate the relationship between insulin, the renin-aldosterone system and blood pressure in obese subjects. DESIGN AND METHODS: A cross sectional study of a group of severely obese normotensive subjects who were surgical candidates (n=39; mean BMI: 47.8+/-1.4) and a group of hypertensive patients (n=57; mean BMI: 28.0+/-0.7) twenty-nine of whom had BMI>27. All subjects were studied after 15 days on a balanced diet. Insulin, plasma renin activity and aldosterone were measured. RESULTS: Fasting insulin, plasma renin activity and aldosterone were higher in severely obese normotensive subjects than in hypertensive subjects (respectively 32.3+/-3.0 vs 13.1+/-1.0 mU/l, P=0.0001; 1.34+/-0.22 vs 0.88+/-0.12 ng/ml/h, P=0.04; 137.2+/-16.2 vs 87.9+/-12.1 pg/ml, P=0.015). Insulin was related to BMI and to aldosterone both in normotensive and in hypertensive patients. CONCLUSION: Hyperinsulinemia itself does not determine hypertension; in some people it could play a vasodilator role in opposition to the renin-aldosterone system.     

Impact of NO-synthase inhibition on renal hemodynamics in normotensive and hypertensive subjects

OBJECTIVE : To examine the acute effects of NO-synthase inhibition on renal hemodynamics in normotensive and hypertensive subjects. METHODS : Changes of renal plasma flow (RPF) and glomerular filtration rate (GFR) in response to intravenous infusions of NG-monomethyl-l-arginine (l-NMMA) (3 mg/kg per 30 min) were measured in 32 normotensive and in 39 essential hypertensive patients by use of clearance technique. RESULTS : l-NMMA significantly decreased RPF in normotensive and hypertensive individuals (P < 0.001), while GFR was preserved. Changes of renal hemodynamic parameters were similar in hypertensive and normotensive subjects (deltaRPF: -88 +/- 89 versus -81 +/- 105 ml/min, P = NS; deltaGFR 1.6 +/- 8.2 versus 4.3 +/- 8.9 ml/min, P = NS) Furthermore, l-NMMA increased mean arterial pressure (deltaMAP 5.3 +/- 6.3 versus 6.0 +/- 6.1 mmHg, P = NS) and decreased heart rate (deltaHR -5.8 +/- 3.9 versus -4.1 +/- 3.8 beats/min, P = NS) to a similar extent in both groups. CONCLUSION : Basal NO synthesis of the renal vasculature is not impaired in patients with established essential hypertension.     

Salt sensitivity in blacks. Salt intake and natriuretic substances

Accumulating evidence suggests that hypertension in blacks is manifested in part by impaired renal excretion of salt. Consequently, this study was performed to determine if hypertensive and normotensive black subjects differ in their ability to generate known natriuretic substances. Fourteen normotensive and 11 hypertensive blacks were maintained on constant metabolic diets containing either 40 or 180 mmol of salt per day for 14 days each. During the last 4 days of each salt intake period, urine was collected for measurement of sodium, dopamine, and norepinephrine. On the last day of each 14-day dietary period, blood pressures were measured, blood was collected for measurement of plasma atrial natriuretic factor (ANF) and aldosterone, and urine was collected over 2 hours for measurement of prostaglandin E2 (PGE2). Both the normotensive and the hypertensive groups manifested salt sensitivity; their mean arterial pressure rose by 7 +/- 0.2 and 6 +/- 0.2%, respectively, when salt intake was increased from 40 to 180 mmol/day. The hypertensive group exhibited decreased (p less than 0.05) dopamine excretion as compared with the normotensive group for both dietary salt intakes. Plasma ANF levels increased (p less than 0.05) in the hypertensive group, but not in the normotensive group, with increasing dietary salt. Plasma aldosterone and urinary norepinephrine and PGE2 were comparable in the two groups for both dietary salt intakes. These data suggest that salt sensitivity is not unique to hypertensive blacks but occurs in normotensive blacks as well. Decreased renal production of dopamine may be a pathogenic factor in the development and maintenance of hypertension in blacks.     

Hydronephrosis causes salt-sensitive hypertension in rats

BACKGROUND: Hypertension is a common disease in the Western world and approximately 5% of all cases are secondary to kidney malfunction. It is not clear whether unilateral hydronephrosis due to partial obstruction affects blood pressure. AIM: The aim of this study was to determine whether hypertension develops and to investigate the effects of different salt diets on the blood pressure in hydronephrotic animals. METHODS: Unilateral partial ureteral obstruction was created in 3-week-old Sprague-Dawley rats. A telemetric device was implanted 4-6 weeks later and blood pressure was measured on normal, low- and high-salt diets. Plasma samples were collected on all diets for renin analysis. RESULTS: All hydronephrotic animals developed hypertension that correlated to the degree of hydronephrosis. The blood pressure increased slowly with time and was salt sensitive. In severe hydronephrosis, blood pressure increased from 118 +/- 5 mmHg on low salt to 140 +/- 6 mmHg on high salt intake, compared to control levels of 82 +/- 2 and 84 +/- 2 mmHg, respectively. Plasma renin concentration was increased in the hydronephrotic group of animals compared to controls on all diets, but the difference was only significant on a normal salt diet, 165 +/- 15 versus 86 +/- 12 microGU/ml respectively. In animals with severe hydronephrosis the plasma renin levels were lower, and the changes less, than in those with mild and moderate hydronephrosis. CONCLUSION: This study demonstrates the presence of a salt-sensitive hypertension in hydronephrosis. A systemic effect of the renin-angiotensin system alone cannot be responsible for the hypertension.     

Plasma ProANP(1-30) reflects salt sensitivity in subjects with heredity for hypertension

The aim of the present study was to investigate whether plasma concentration of proANP(1-30), the N-terminal fragment of the atrial natriuretic peptide prohormone, or 24-hour urinary excretion of urodilatin reflects the degree of salt sensitivity in hypertension-prone individuals. Plasma concentration of proANP(1-30) and urinary urodilatin excretion were determined at baseline, after 1 week on a low-salt diet (10 mmol/d) and after another week on a high-salt diet (240 mmol/d) in 30 healthy subjects with heredity for hypertension. Salt sensitivity was defined as the difference between mean arterial blood pressure after the high-salt diet and the mean arterial blood pressure after the low-salt diet. High- versus low-salt intake increased proANP(1-30) (668+/-330 versus 358+/-150 pmol/L; P<0.00001) and urodilatin (18.7+/-5.2 versus 16.0+/-8.3 pmol/24 h; P<0.05). ProANP(1-30) correlated with salt sensitivity at baseline (r=0.76, P<0.000001), after the low- (r=0.80, P<0.0000001) and high-salt diets (r=0.85, P<0.00000001). The increase in proANP(1-30) induced by changing from the low- to the high-salt diet was also directly related to salt sensitivity (r=0.78, P<0.000001). ProANP(1-30) was not related to urinary sodium excretion. Neither urodilatin nor the sodium-induced change in urodilatin correlated with salt sensitivity. However, urodilatin was related to the urinary sodium excretion at baseline (r=0.58, P<0.01) and after the high-salt diet (r=0.62, P<0.001). In conclusion, the close correlations between proANP(1-30) and salt sensitivity suggest that proANP(1-30) may serve as a marker for salt sensitivity and could be useful in identifying subjects who would benefit from dietary salt restriction to prevent development of hypertension.