The Sodium Intake Modifies the Renin-Aldosterone and Blood Pressure Changes Associated with Moderately Low Energy Diets

ABSTRACT. Thirty middle-aged, moderately obese men with untreated mild hypertension were allocated to two groups of 15 men each. Both groups were placed on energy-reduced diets (5.1 MJ/day) for 9–11 weeks which resulted in similar losses of body mass (8.5 kg). In group I the low energy diet was supplemented with sodium chloride leading to no change in urinary sodium excretion. During dieting there were significant reductions of plasma renin activity (PRA) and urinary excretion of noradrenaline and aldosterone. Heart rate but not mean arterial pressure (MAP) decreased significantly. Then followed a period of sodium restriction which resulted in a significant decrease in MAP and an increase in aldosterone excretion. In group II there was a reduction of sodium intake by about 80 mmol as judged from determinations of urinary sodium excretion. In this group the energy restriction was not accompanied by any changes in PRA or urinary excretion of aldosterone, whereas urinary noradrenaline excretion, heart rate and MAP decreased significantly. Urinary adrenaline excretion remained unchanged. It is concluded that the hypotensive response to moderate energy and sodium reduction cannot be explained by changes in the renin-aldosterone system.     

Stress and High Sodium Effects on Blood Pressure and Brain Catecholamines in Spontaneously Hypertensive Rats

The following experiments were designed to determine if territorial stress, dietary sodium (Na), or the combination of stress and Na effect the rate of development of hypertension in the spontaneously hypertensive rat (SHR 4-18 wks) and if central catecholamines (C) were altered by these treatments. BP was significantly elevated from 2-8 weeks of stress treatment as compared to SHR controls. Norepinephrine (NE) levels in the nucleus tractus solitarius and amygdala (A), and dopamine (D) levels in the hippocampus and A showed significant elevations in the stressed group. High Na (3%) treatment combined with stress treatment produced an even further BP increase and elevated D levels in the amygdala, and elevated NE levels in the area postrema as compared to control SHR's. Selected brain C variables were able to correctly classify animals into high and low BP groups with 90-100% accuracy. Our data support the concept that there are important stress and Na effects upon brain neurochemistry which influence the development of hypertension in the SHR.     

Blood Pressure and Sodium Excretion in the Sinoaortic Denervated Rat During Chronic High and Low Sodium Intake and Acute Sodium Loading

We studied the effects of dietary sodium on the magnitude of hypertension in sinoaortic denervated (SAD) rats. Groups of SAD rats and sham operated (SO) controls drank tap water and received chows with different amounts of sodium: low (0.08%), regular (0.4%), high (3%) or very high (7%) sodium; other groups, some after unilateral nephrectomy, received regular chow and 1% saline to drink. These various sodium regimens were started before operations and were continued for at least 12 weeks after SAD and SO. Weekly systolic tail-cuff pressures of SAD rats were significantly higher throughout the 12 week postoperative period than those of SO rats regardless of sodium regimen (p<0.05 to<0.01). Analysis of variance indicated no significant differences between pressures of SAD rats on regular or low sodium chows and those receiving any of the high sodium regimens. When SAD rats were switched from regular to high sodium diets no significant change was induced in systolic pressures. We then examined renal sodium excretion in response to oral sodium loading or to intravenous saline infusion in groups of SAD and SO rats. Both types of studies revealed that SAD rats excreted the extra sodium significantly faster than SO rats. We conclude that hypertension induced by SAD is not dependent on the amount of sodium in the diet and that the magnitude of hypertension is not increased by chronic high sodium intake. The rapid excretion of sodium suggests SAD rats have an enhanced sensitivity t o activation and/or to effects of neural and/or humoral factors affecting renal sodium excretion.     

Sodium and Hypertension: Effect of Dietary Calcium Supplementation on Blood Pressure

Normotensive female Wistar Kyoto rats were studied to examine the effects of replacing drinking water with highly palatable saline solution at a concentration (0.5%) close to the maximum preferred concentration in these animals. A further group of animals was offered a calcium-supplemented diet in addition to substitution of drinking water with saline. Fluid consumption in animals drinking tap water was constant at between 35–40 ml/day throughout the six-month study period. In contrast, animals drinking 0.5% saline consumed 75–85 ml/day throughout the study period, irrespective of the calcium content of the diet. Voluntary consumption of these quantities of saline was associated with the development of a moderate hypertension, measured by tail cuff plethysmography, after two months of study. However, in animals consuming calcium-supplemented diets the hypertensive response disappeared after 3 months of study. Blood pressures were validated at the conclusion of the study by direct arterial cannulation and confirmed the presence of hypertension in saline drinking animals only when diets lacked calcium supplementation. No changes in blood ionized sodium concentration were associated with saline consumption; however, blood ionized calcium was significantly reduced in animals drinking saline, but not when calcium-supplemented diet was available. These studies suggest an interaction between sodium and calcium in the genesis of sodium-dependent hypertension.     

The Bergen Blood Pressure Study: Sodium Intake and Ambulatory Blood Pressure in Offspring of Hypertensive and Normotensive Families

Sodium intake, estimated by the 24-h urine sodium excretion, was assessed in 39 offspring of hypertensive families and 37 offspring of normotensive families. The family history of hypertension or normotension was defined according to parental BP data from two surveys conducted 27 years apart. Urine sodium excretion was similar in offspring of hypertensive and normotensive families, averaging 136 and 137 mmol/24 h, respectively. Monitored by non-invasive methodology in the urine sampling period, the average 24-h ambulatory blood pressure (BP) was approximately 10/10 mmHg higher in offspring of hypertensive than normotensive families. The clinically and statistically significant differences in BP between groups could not be explained by differences in sodium intake. After adjustment for confounding variables, the BP was not associated with the sodium excretion in the material as a whole or in either offspring group.     

Effect of Hydralazine on Serial Measurements of Exchangeable Sodium and Blood Pressure in Spontaneously Hypertensive Rats

Hydralazine was dissolved in 0.5% drinking saline (40 mg/1000 ml) labelled with isotope ²²Na and given to spontaneously hypertensive rats for four weeks. Another group of rats were given isotope labelled saline only and served as control. Measurements of total exchangeable sodium, blood pressure, pulse rate and weight were performed before and repeatedly during treatment. Before treatment exchangeable sodium, blood pressure, pulse rate, and weight were no different between the groups. The antihypertensive effect of hydralazine was marked and maintained throughout the experiment. No significant changes were found in pulse rate. Both groups gained weight similarly. Exchangeable sodium increased at the same rate in both groups along with the weight increase. Thus, chronic hydralazine treatment effectively reduces blood pressure in spontaneously hypertensive rats without causing measurable sodium or fluid retention.     

Sodium Elimination Rate and Blood Pressure during Normal and High Salt Intake in Subjects with and without Familial Predisposition to Hypertension

Abstract We have assessed the elimination rate of ²²Na (ER-²²Na), total exchangeable sodium (Na^E), blood pressure, plasma volume (PV), haematocrit, urinary noradrenaline (U-NA) and urinary 3-methoxy-4-hydroxymandelic acid (U-VMA) in normotensive men with (n=17) and without (n=15) familial predisposition to hypertension. All measurements were done during habitual salt intake and after four weeks of increased salt intake (ordinary intake + 12 g NaC1/daily). On ordinary salt intake, ER-²²Na, Na^E, blood pressure, PV, haematocrit, U-NA and U-VMA did not differ between the groups thus indicating a normal sodium turnover in both groups and a comparable activity of the sympathetic nervous system. After 10 days of high salt intake those without familial predisposition showed signs of volume expansion and decreased sympathetic activity and those with such predisposition showed insignificant changes in the same direction. After four weeks of increased salt intake, ER-²²Na had increased significantly and equally in both groups, while blood pressure and Na^E remained unchanged. This indicates that the predisposed individuals had a normal ability to cope with a prolonged increase in salt intake.     

Impact of Dialysate Sodium Concentration Lowering on Home Blood Pressure Variability in Hemodialysis Patients

Blood pressure variability is an independent risk factor for mortality and cardiovascular events in hemodialysis patients. Dialysate sodium concentration may not only have effects on blood pressure but also on blood pressure variability. We investigated whether dialysate sodium concentration lowering could decrease home blood pressure variability in hemodialysis patients. Forty‐three hemodialysis patients at their dry weight assessed by bioimpedance methods with pre‐dialysis serum sodium >136 mmol/L were recruited. Firstly, patients underwent a 1‐month standard dialysis with dialysate sodium concentration of 138 mmol/L, and then the dialysate sodium concentration was decreased to 136 mmol/L for 8 weeks. Home blood pressure was assessed on waking up and at bedtime for 1 week. Coefficient of variation was used to define home blood pressure variability. After the intervention, whole‐day systolic blood pressure variability decreased from 5.7 ± 2.6% to 4.3 ± 1.7% and evening systolic blood pressure variability decreased from 7.9 ± 4.1% to 6.2 ± 3.1%. Morning systolic blood pressure variability had a reduction from 7.8 ± 2.4% to 5.9 ± 3.3% but did not achieve statistical significance (P = 0.077). Whole‐day, morning and evening systolic blood pressure were decreased significantly. Less changes were observed in diastolic blood pressure parameters. Interdialytic weight gain mildly but significantly decreased. Volume parameters, dietary sodium intake and incidence of adverse events were similar throughout the study period. Lowering dialysate sodium concentration could improve home blood pressure variability among hemodialysis patients who had achieved their dry weight.     

Dietary Sodium Intake and Urinary Dopamine and Sodium Excretion During the Course of Blood Pressure Development in Dahl Salt-Sensitive and Salt-Resistant Rats

ABSTRACT

Recent studies have suggested that dopamine (DA) formed within the kidney may play an important role in promoting sodium excretion, and that renal production and excretion of DA is determined by dietary sodium intake. Inasmuch as increased sodium consumption produces hypertension in Dahl salt-sensitive (DS) rats but not in Dahl salt-resistant (DR) rats, the present study was designed to examine the relationship between sodium consumption and urinary excretion of DA in these rats. DS and DR rats were placed on either high sodium chloride (8%) or low sodium chloride (0. 4%) diets at 4 weeks of age and their systolic blood pressure (SBP), urine volume, urinary sodium and catecholamine excretion were measured once every week for the next 4 weeks. High sodium chloride diet increased SBP in DS rats at 6 weeks of age and SBP continued to rise until they were 8 weeks old. The SBP of DR rats did not reach hypertensive levels when they were given high sodium chloride diet. The SBP of DS rats on low sodium chloride diet was significantly higher than DR rats on the same diet. The urinary DA excretion increased with age in all four groups of rats and was similar when they were 8 weeks old. However, both DS and DR rats on high sodium chloride diet excreted greater amounts of sodium and had increased urine volume compared to the DS and DR rats on low sodium chloride diet. There were no significant differences in urinary NE or E excretion in these four groups of rats. Kidney levels of DA and NE were significantly lower in DS compared to DR rats on high sodium chloride diet. These results show that although there are no differences in urinary DA excretion between rats on low and high sodium intake, both DS and DR rats on high sodium chloride diet are able to exhibit a natriuretic response. The DS rats eliminate sodium at the expense of an elevated SBP whereas DR rats stay normotensive. Therefore, it appears that alterations in mechanisms controlling renal vascular resistance rather than sodium excretion are responsible for the development of hypertension in DS rats.     

Body Composition,Intraerythrocyte Sodium Content,Volume Regulation and Blood Pressure during Moderate Sodium Restriction in Hypertensive Men

ABSTRACT. Eleven moderately obese middle-aged male outpatients with untreated mild hypertension reduced their sodium intake by about 120 mmol per day during 4–6 weeks. Diastolic blood pressure was then significantly reduced in comparison with a matched control group. The reduction of urinary sodium excretion was significantly correlated to the change in mean arterial pressure. Mean body mass showed a small significant decrease, although there were no significant changes in total body water or body fat as determined from measurements of ⁴⁰K and tritiated water. Nor did mean extracellular water or plasma volume (Evan's blue) show any significant change. The decrease in urinary sodium excretion was associated with increases in plasma renin activity and urinary aldosterone excretion, while a sympathetic nervous natriuretic index (urinary dopamine to noradrenaline excretion ratio) decreased. The low sodium diet period was followed by a period of energy reduction as well as sodium restriction for 15 weeks. Mean body mass was then reduced by about 8 kg. The systolic but not the diastolic blood pressure showed a significant decrease. The intraerythrocyte content of water, sodium and potassium did not change significantly during any of the diet periods. We conclude that moderate sodium restriction lowered the blood pressure and affected the renin-aldosterone and sympathetic nervous system to retain sodium which might explain the constancy of the plasma volume.     

Effect of High Blood Pressure Stress on Vascular Adrenergic Responsiveness in the Spontaneously Hypertensive Rat

A model in which partial ligation of the left external iliac artery results in a decrease in mean arterial blood pressure to the ipsilateral femoral artery (70 mmHg; protected) while mean pressure increases in the contralateral femoral artery (125 mmHg; unprotected) was used to determine the effect of high blood pressure stress on vascular adrenergic responsiveness. Age-matched (5 week old) male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were used in the study. Partial ligation was performed at 6 weeks of age and vascular reactivity studies undertaken at 10 weeks of age when the SHR were considered hypertensive (indirect systolic blood pressure greater than 150 mmHg). Force-tension analysis of femoral arterial rings revealed that all tissues contracted maximally at 1.0 gram of preload force. This value was used in subsequent studies on adrenergic responsiveness. Isoproterenol-induced relaxation was significantly attenuated in rings of vascular smooth muscle from unprotected femoral arteries of the SHR, however, the response of rings from protected arteries of the SHR was similar to that of the protected and unprotected arteries of the WKY animal. Unprotected arteries of the SHR exhibited a greater response to norepinephrine stimulation when compared to protected arteries of the SHR as well as unprotected and protected arteries of the WKY animal. This study suggests that alterations in vascular α-and β-adrenergic responsiveness in the SHR are most probably due to the increase in blood pressure     

Cozaar降压疗效及对靶器官的保护作用

目的探讨血管紧张素Ⅱ受体拮抗剂－Ｃｏｚａａｒ（科素亚）的降压疗效及对心肾靶器官的影响。方法６０例高血压病Ⅱ期患者服用Ｃｏｚａａｒ５０ｍｇ／ｄ～１００ｍｇ／ｄ治疗八周。结果Ｃｏｚａａｒ不仅使血压持续下降,并且逆转心脏左室肥厚,改善心功能,降低尿蛋白排泄量及血尿β２－ＭＧ含量水平（Ｐ＜０．０１）。结论Ｃｏｚａａｒ降压疗效肯定及对高血压靶器官具有保护作用。     

Effects of Sodium Concentration and Dialysate Temperature Changes on Blood Pressure in Hemodialysis Patients: A Randomized,Triple‐Blind Crossover Clinical Trial

The present study investigated the effects of different temperatures and sodium dialysate concentration on blood pressure in hemodialysis patients. Following Williams’ design, hemodialysis patients were randomly assigned into four dialysis modes. Dialysate temperature was set at 37°C for modes A and C and, 35°C for modes B and D. Sodium concentration was set at 138 mmol/L in modes A and B, while it changed from 150 mmol/L to 138 mmol/L in modes C and D. Using analysis of variance for repeated measures, the mean values of systolic and diastolic blood pressure were investigated. The mean values of systolic and diastolic blood pressure in modes C and D had a significant difference with the values in mode A. The mean values of systolic and diastolic blood pressure in patients dialyzed with mode B had a significant difference with the values in those dialyzed with mode D. Moreover, there were significant differences in the incidence of hypotension between A and other modes and between B and modes C and D, but this difference was not significant between modes C and D. In order to reduce intradialytic blood pressure fluctuations and hypotension, the nursing staff are recommended to gradually reduce dialysate sodium concentration.     

Effects of Dietary Sodium and Calcium on Blood Pressure Reactivity in the shr and WKY

Salt-sensitive spontaneously hypertensive rats (SHR) and their normotensive control strain, Wistar-Kyoto rats (WKY) were fed four diets varying in sodium chloride and calcium content in order to assess the effects of diet on learned blood pressure responses. The animals were exposed to a classical conditioning paradigm in which one tone was always followed by a brief electric shock and a second tone was never followed by shock. Sodium chloride loading raised baseline blood pressure in both strains, while supplemental calcium attenuated blood pressure. Sodium chloride potentiated blood pressure orienting responses to initial presentations of the tones among calcium deficient, but not calcium replete SHR. Increased sodium chloride intake also potentiated the learned pressor responses to the tone paired with shock in the SHR, but not the WKY. Calcium intake had no apparent effect on the learned blood pressure responses to the two tones.     

Apelin Effects on Blood Pressure and RAS in DOCA-Salt-Induced Hypertensive Rats

Apelin, a novel multifunctional peptide implicated in the regulation of the cardiovascular system, including blood pressure and cardiac function control, has been postulated to be involved in the pathophysiology of hypertension and hypertensive heart disease. The aim of this study was to investigate, for the first time, whether the effects of apelin’s chronic application might be involved in deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats). In this study, 8–10-week-old male Wistar rats were divided into four groups: control, control + apelin, DOCA-salt rats, DOCA-salt rats + apelin. Deoxycorticosterone Acetate (25 mg/kg of body weight) was injected subcutaneously, twice a week for 4 weeks. These rats received NaCl 1% instead of tap water for drinking during the experimental period. Later, rats were randomly treated with pyroglutamylated apelin-13 (200 μg. kg^?1. day^?1 intraperitonealy) for 17 days. The concentrations of apelin, endothelin-1, angiotensin-converting enzyme, angiotensinogen, and angiotensin II were analyzed in the plasma. The mRNA level of apelin and apelin receptor were determined in the heart and aorta tissue by real-time polymerase chain reaction, respectively. It was found that apelin reduces blood pressure in DOCA-salt rats. Apelin can be used as a therapeutic agent in the treatment of hypertension in the future.     

N-乙酰半胱氨酸对自发性高血压大鼠血压及相关因素的影响

目的探讨应用NAC治疗对高血压的影响。方法雄性自发性高血压大鼠(n=30),随机分成N-乙酰半胱氨酸组、安慰剂组和基础组三组,基础组入选后即处死留取血标本检测。N-乙酰半胱氨酸组和安慰剂组测量实验前后收缩压,并检测大鼠血清NO含量及白细胞介素1含量。结果实验结束时N-乙酰半胱氨酸组血压明显低于安慰剂组(P<0.05)。N-乙酰半胱氨酸组血浆NO浓度明显高于安慰剂组(P<0.05)。N-乙酰半胱氨酸组白细胞介素1含量低于安慰剂组(P<0.05)。结论大鼠饮用含N-乙酰半胱氨酸(10g/L)自来水能降低血压,提高血浆NO和降低白细胞介素1含量,对大鼠心血管系统有保护作用。     

The Effect of Metformin and Insulin on Sympathetic Nerve Activity, Norepinephrine Spillover and Blood Pressure in Obese, Insulin Resistant, Normoglycemic, Hypertensive Men

To evaluate the effect of metformin on insulin sensitivity and to further examine the relationship between insulin resistance, sympathetic nerve activity and blood pressure, 6 obese insulin resistant, normoglycemic hypertensive men were investigated (age 49 ± 2 years, BMI 27.6 ± 1.2, mean ± SEM). The study had a placebo controlled, double blind, cross over design with 6 weeks' metformin treatment (850 mg b.i.d) vs placebo. Blood pressure was measured weekly. At the end of each treatment period, glucose infusion rate (GIR), muscle sympathetic nerve activity (MSA) and renal and total body norepinephrine (NE) kinetics (radioisotope dilution) were examined during euglycemic hyperinsulinemic clamp. Fasting insulin was 13 ± 3 and 10 ± 2 mU/l and fasting glucose 5.3 ± 0.2 and 5.1 ± 0.1 mmol/l after placebo and metformin treatment, respectively (ns). GIR during the last hour of the insulin clamp was 3.7 ± 0.6 vs 3.6 ± 0.6 mg/kg x min (ns). Resting MSA, total body and right renal NE spillover did not differ significantly after placebo and metformin treatment. Systolic and diastolic blood pressures were 151 ± 10/95 ± 5 mmHg after placebo and 146 ± 5/94 ± 5 mmHg after metformin treatment (ns). Thus metformin treatment did not have any significant effect on insulin sensitivity, blood pressure or sympathetic activity in this small group of patients. Renal plasma flow and MSA increased significantly during the insulin clamp, whereas renal NE and total body NE spillover remained unchanged, suggesting nonuniform regional sympathetic nerve responses to acute hyperinsulinemia.     

正压通气治疗对OSAHS患者EBC和血清中去甲肾上腺素水平的影响

目的探讨auto—CPAP治疗对OSAHS患者交感神经兴奋性的影响。方法根据PSG确诊的42例OSAHS患者,随机分为治疗组和对照组,对治疗组进行auto—CPAP治疗,对所有患者采取常规治疗,测定治疗组及对照组治疗前后EBC和血清中的NE。结果（1）治疗组患者EBC和血清中NE治疗前高于治疗后（P〈0．01）;（2）对照组患者EBC和血清中NE治疗前后无统计学意义（P〉0．05）;（3）OSAHS患者EBC和血清中NE水平与AHI呈正相关关系,与LPS02、MPS02呈负相关关系（P〈0．叭）。结论OSAHS患者常伴有交感神经兴奋性的增强,并且可以通过auto．CPAP治疗得以改善。     

Angiotensin Converting Enzyme Inhibition Reveals an Important Role for the Renin System in the Control of Normal and High Blood Pressure in Man

Captopril, given for 5 days to normotensive healthy subjects caused a significant fall in blood pressure. The fall in mean supine blood pressure was greater on a low sodium diet (10 mmols/ day) - 19.6% and was less on a high sodium diet (350 mmols/day) - 11% compared to the normal sodium intake (120 mmols/day) when the fall in blood pressure was 16.5%. Patients with essential hypertension who were studied on their normal diet had a similar fall in blood pressure for a given plasma renin activity. It seems likely that the predominant mechanism whereby captopril lowers blood pressure is through the inhibition of the formation of angiotensin II. If this is so, our results suggest that the renin system is an important control of both normal and high blood pressure when on a normal sodium intake.