Beta blockade,diuretics, and salt restriction for the management of mild hypertension: a randomised double blind trial.

Ninety four patients with mild hypertension (average supine diastolic blood pressure (phase V) 95-110 mm Hg) were allocated at random to receive restriction of dietary sodium (maximum allowed 70 mmol(mEq)/24 h) or a normal diet. In addition, they received in random order 25 mg chlorthalidone, 200 mg metoprolol (slow release), and a fixed combination of these two drugs. Each drug treatment was given for four weeks and alternated with four weeks of placebo. Forty four patients were allocated to sodium restriction (group 1) and 50 to normal diet (group 2). The mean 24 hour urinary sodium excretion in group 1 was 74 (SD 31) mmol(mEq)/24 h, and in group 2 132 (51) mmol/24 h. Compared with the screening blood pressure the average decrement of the supine blood pressure in group 1 was 16.0/8.6 mm Hg with placebo, 21.7/11.5 mm Hg with the diuretic, 28.5/17.8 mm Hg with the beta blocker, and 28.9/18.4 mm Hg with the combined agent; in group 2 these values were 13.3/6.1, 20.3/9.7, 21.3/12.9, and 29.4/16.8 mm Hg, respectively. There was a sharp decrease of the average potassium concentration during chlorthalidone and combination treatment periods (average value 3.3 mmol(mEq)/1). These results suggest that moderate salt restriction used as sole treatment has a limited though demonstrable blood pressure lowering effect but that when it is used as an adjuvant to beta blocker treatment its value is greatly enhanced.     

Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation.

OBJECTIVE--To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN--Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING--Patients attending diabetic outpatient clinic of city hospital. PATIENTS--Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS--After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT--Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS--Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS--Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.     

Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study.

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month''s treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.     

Moderate potassium chloride supplementation in essential hypertension: is it additive to moderate sodium restriction?

Twenty patients with mild or moderate essential hypertension and not receiving any drug treatment, who had been moderately restricting their sodium intake to around 70 mmol(mEq) a day for at least one month and whose mean blood pressure was then 163/103 mm Hg, were entered into a double blind, randomised crossover study to compare one month''s treatment with slow release potassium chloride tablets (64 mmol potassium chloride a day) with one month''s treatment with a matching placebo. Mean (SEM) urinary sodium excretion on entry to the study was 68 (6.8) mmol/24 h. Mean urinary potassium excretion increased from 67 (6.9) mmol(mEq)/24 h with placebo to 117 (4.6) mmol/24 h with potassium chloride. Supine and standing systolic and diastolic blood pressures did not change significantly with potassium chloride supplementation when compared with pressures while receiving placebo or before randomisation. In patients who are able moderately to restrict their sodium intake doubling potassium as a chloride salt has little or no effect on blood pressure.     

Efficacy of potassium and magnesium in essential hypertension: a double-blind,placebo controlled,crossover study.

OBJECTIVE--To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension. DESIGN--A double blind, randomised, placebo controlled, crossover trial of 32 weeks'' duration. SETTINGS--Cardiology outpatient department, Sassoon General Hospitals, Pune, India. PATIENTS--37 Adults with mild hypertension (diastolic blood pressure less than 110 mm Hg). INTERVENTION--Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design. No other drug treatment was allowed. MEASUREMENTS--Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals. RESULTS--Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures (p less than 0.001) and a significant reduction in serum cholesterol concentration (p less than 0.05); other biochemical variables did not change. Magnesium did not have an additional effect. Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium. The drug was well tolerated and compliance was satisfactory. CONCLUSION--Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension. Giving magnesium as well has no added advantage.     

Dietary sodium restriction for mild hypertension in general practice.

Eighteen patients with stable mild hypertension (mean blood pressure 144/93 mm Hg) restricted their sodium intake for eight weeks while taking part in a double blind randomised crossover trial of slow sodium and placebo tablets. Mean 24 hour urinary sodium excretion was 143 mmol(mEq) during the period on slow sodium and 87 mmol during the period on placebo. Five patients were unable to reduce their sodium intake below 120 mmol, but the others had a mean 24 hour urinary sodium excretion of 59 mmol during the period on placebo. There was no significant difference in blood pressure between the slow sodium and placebo treatment periods, although the study had a power of 99% to detect a difference of 5 mm Hg in mean arterial pressure between the two periods. Moderate dietary sodium restriction does not lower blood pressure in patients with this degree of hypertension.     

Lack of effect of oral magnesium on high blood pressure: a double blind study.

Seventeen unselected patients with mild to moderate essential hypertension and whose average supine blood pressure after two months'' observation with no treatment was 154/100 mm Hg were entered into a double blind randomised crossover study of one month''s treatment with magnesium aspartate (15 mmol magnesium/day) and treatment with placebo for a further month. This preparation of magnesium was well tolerated and did not cause diarrhoea. Despite a significant increase in plasma magnesium concentration and a significant increase in urinary excretion of magnesium while taking magnesium aspartate there was no fall in blood pressure compared with either treatment with placebo or values before treatment. The results provide no evidence for a role of dietary magnesium in the regulation of high blood pressure and are contrary to recent speculations.     

Controlled trial of long term oral potassium supplements in patients with mild hypertension.

A 15 week randomised double blind placebo controlled trial of oral potassium supplements (48 mmol daily) was conducted in 37 patients who had mildly increased blood pressure and a normal dietary intake of sodium. After a two month run in and a one week baseline period the patients were randomly assigned to receive either potassium supplements (n = 18) or placebo (n = 19). By the third week of treatment blood pressure in the actively treated group had decreased significantly compared with that in the placebo group, though the decrease reached its maximum after 15 weeks. Urinary potassium excretion increased significantly in the group who received potassium supplements, but no significant changes were found in plasma sodium and potassium concentrations or in urinary sodium excretion. In a subgroup of 13 patients who underwent a further nine weeks of treatment with oral potassium supplements at half of the previous dose (24 mmol daily) their blood pressure, at the end of this second study period, was still significantly lower compared with their baseline value but not with that of the placebo group. These results show that moderate oral potassium supplements are associated with a long term reduction in blood pressure in patients who have mild hypertension.     

Relation between arterial pressure,dietary sodium intake,and renin system in essential hypertension.

Forty-one patients with mild essential hypertension, 36 patients with severe hypertension, and 28 normotensive subjects were studied on a high sodium intake of 350 mmol/day for five days and low sodium intake of 10 mmol/day for five days. The fall in mean arterial pressure on changing from the high-sodium to the low-sodium diet was 0.7 +/- 1.7 mm Hg in normotensive subjects, 8 +/- 1.4 mm Hg in patients with mild hypertension, and 14.5 +/- 1.4 mm Hg in patients with severe hypertension. The fall in blood pressure was not correlated with age. Highly significant correlations were obtained for all subjects between the ratio of the fall in mean arterial pressure to the fall in urinary sodium excretion on changing from a high- to a low-sodium diet and (a) the level of supine blood pressure on normal diet, (b) the rise in plasma renin activity, and (c) the rise in plasma aldosterone. In patients with essential hypertension the blood pressure is sensitive to alterations in sodium intake. This may be partly due to some change either produced by or associated directly with the hypertension. A decreased responsiveness of the renin-angiotensin-aldosterone system shown in the patients with essential hypertension could partly account for the results.     

Sodium and potassium intake and blood pressure change in childhood.

OBJECTIVE--To assess the association between sodium and potassium intake and the rise in blood pressure in childhood. DESIGN--Longitudinal study of a cohort of children with annual measurements during an average follow up period of seven years. SETTING--Epidemiological survey of the population of a suburban town in western Netherlands. SUBJECTS--Cohort of 233 children aged 5-17 drawn at random from participants in the population survey. MAIN OUTCOME MEASURES--At least six annual timed overnight urine samples were obtained. The mean 24 hour sodium and potassium excretion during the follow up period was estimated for each participant and the sodium to potassium ratio calculated. Individual slopes of blood pressure over time were calculated by linear regression analysis. RESULTS--No significant association was observed between sodium excretion and the change in blood pressure over time. The mean systolic blood pressure slopes, however, were lower when potassium intake was higher (coefficient of linear regression -0.045 mm Hg/year/mmol; 95% confidence interval -0.069 to -0.020), and the change in systolic pressure was greater when the urinary sodium to potassium ratio was higher (0.356 mm Hg/year/unit; 95% confidence interval 0.069 to 0.642). In relation to potassium this was interpreted as a rise in blood pressure that was on average 1.0 mm Hg (95% confidence interval -1.65 to -0.35) lower in children in the upper part of the distribution of intake compared with those in the lower part. The mean yearly rise in systolic blood pressure for the group as a whole was 1.95 mm Hg. Urinary electrolyte excretion was not associated with diastolic blood pressure. CONCLUSION--Dietary potassium and the dietary sodium to potassium ratio are related to the rise in blood pressure in childhood and may be important in the early pathogenesis of primary hypertension.     

Effect of magnesium on blood pressure.

Twenty patients receiving long term diuretic treatment for arterial hypertension (18 patients) or congestive heart failure (two patients) received magnesium supplementation as aspartate hydrochloride 15 mmol/day for six months. Both systolic and diastolic pressures decreased significantly, by a mean of 12/8 mm Hg. No significant changes were recorded in plasma or urinary electrolytes except for magnesium, 24 hour urinary volumes, or body weight after treatment. The effect of magnesium on blood pressure may be direct or through influences on the internal balance of potassium, sodium, and calcium.     

Endpiece: Hospital league tables 1830

ObjectiveTo assess the long term effects of advice to restrict dietary sodium in adults with and without hypertension.DesignSystematic review and meta-analysis of randomised controlled trials.OutcomesMortality, cardiovascular events, blood pressure, urinary sodium excretion, quality of life, and use of antihypertensive drugs.ResultsThree trials in normotensive people (n=2326), five trials in those with untreated hypertension (n=387), and three trials in people being treated for hypertension (n=801) were included, with follow up from six months to seven years. The large high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported. There were 17 deaths, equally distributed between intervention and control groups. Systolic and diastolic blood pressures were reduced (systolic by 1.1 mm Hg, 95% confidence interval 1.8 to 0.4 mm Hg; diastolic by 0.6 mm Hg, 1.5 to −0.3 mm Hg) at 13 to 60 months, as was urinary 24 hour sodium excretion (by 35.5 mmol/24 hours, 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related.ConclusionsIntensive interventions, unsuited to primary care or population prevention programmes, provide only small reductions in blood pressure and sodium excretion, and effects on deaths and cardiovascular events are unclear. Advice to reduce sodium intake may help people on antihypertensive drugs to stop their medication while maintaining good blood pressure control.

What is already known on this topic

Restricting sodium intake in people with hypertension reduces blood pressureLong term effects (on blood pressure, mortality, and morbidity) of reduced salt intake in people with and without hypertension are unclear

What this study adds

Few deaths and cardiovascular events have been reported in salt reduction trialsMeta-analysis shows that blood pressure was reduced (systolic by 1.1 mm Hg, diastolic by 0.6 mm Hg) at 13 to 60 months, with a reduction in sodium excretion of almost a quarter (35.5 mmol/24 hours)The interventions used were highly intensive and unsuited to primary care or population prevention programmesLower salt intake may help people on antihypertensive drugs to stop their medication while maintaining good control of blood pressure, but there are doubts about effects of sodium reduction on overall health     

Effect of various chloride salts on the utilization of phosphorus, calcium, and magnesium

Only part of the effect of dietary protein on urinary calcium excretion can be ascribed to sulfur amino acids. We hypothesized that chloride, another factor often associated with isolated proteins, and another amino acid, lysine, affect utilization of calcium. The effects of supplemental dietary chloride, inorganic or organic, on calcium, phosphorus, and magnesium utilization were studied in two rat studies. Weanling Sprague-Dawley rats were fed semi-purified diets that contained moderate (1.8 mg Cl/g diet) or supplemental (15.5 mg Cl/g diet) chloride as sodium chloride, potassium chloride, or lysine monohydrochloride with or without calcium carbonate for 56 or 119 days. Rats fed supplemental sodium chloride or potassium chloride had higher urinary phosphorus excretion, more efficient phosphorus absorption, but unchanged tissue phosphorus levels after 7 and 16 weeks of dietary treatment as compared to rats fed moderate chloride. Rats fed supplemental sodium chloride or potassium chloride excreted more calcium in urine at 7 weeks and absorbed calcium less efficiently at 16 weeks. Tissue calcium concentrations were unaffected, but total tibia magnesium and plasma magnesium concentrations were lower in rats fed supplemental sodium chloride or potassium chloride than those fed moderate chloride. Lysine chloride with or without additional calcium elevated urinary calcium excretion even more than sodium chloride and potassium chloride ingestion. Rats fed lysine chloride with supplemental calcium had smaller apparent absorption and urinary losses of phosphorus and magnesium after 16 weeks and lower tibia and plasma magnesium concentrations than rats fed lysine chloride.     

Relation between dose of bendrofluazide,antihypertensive effect,and adverse biochemical effects.

OBJECTIVE--To determine the relevant dose of bendrofluazide for treating mild to moderate hypertension. DESIGN--Double blind parallel group trial of patients who were given placebo for six weeks and then randomly allocated to various doses of bendrofluazide (1.25, 2.5, 5, or 10 mg daily) or placebo for 12 weeks. SETTING--General practices in Zealand, Denmark. PATIENTS--257 Patients with newly diagnosed or previously treated hypertension, aged 25-70, who had a mean diastolic blood pressure of 100-120 mm Hg after receiving placebo for six weeks. MAIN OUTCOME MEASURES--Reduction in diastolic blood pressure and changes in biochemical variables (potassium, urate, glucose, fructosamine, total cholesterol, apolipoprotein A I, apolipoprotein B, and triglyceride concentrations). RESULTS--All doses of bendrofluazide significantly reduced diastolic blood pressure to the same degree (10-11 mm Hg). Clear relations between dose and effect were shown for potassium, urate, glucose, total cholesterol, and apolipoprotein B concentrations. The 1.25 mg dose increased only urate concentrations, whereas the 10 mg dose affected all the above biochemical variables. CONCLUSION--The relevant range of doses of bendrofluazide to treat mild to moderate hypertension is 1.25-2.5 mg a day. Higher doses caused more pronounced adverse biochemical effects including adverse lipid effects. Previous trials with bendrofluazide have used too high doses.     

Lifestyle modifications to prevent and control hypertension. 5. Recommendations on dietary salt. Canadian Hypertension Society,Canadian Coalition for High Blood Pressure Prevention and Control,Laboratory Centre for Disease Control at Health Canada,Heart and Stroke Foundation of Canada

OBJECTIVE: To provide updated, evidence-based recommendations concerning the effects of dietary salt intake on the prevention and control of hypertension in adults (except pregnant women). The guidelines are intended for use in clinical practice and public education campaigns. OPTIONS: Restriction of dietary salt intake may be an alternative to antihypertensive medications or may supplement such medications. Other options include other nonpharmacologic treatments for hypertension and no treatment. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period 1966-1996 using the terms hypertension, blood pressure, vascular resistance, sodium chloride, sodium, diet, sodium or sodium chloride dietary, sodium restricted/reducing diet, clinical trials, controlled clinical trial, randomized controlled trial and random allocation. Both trials and review articles were obtained, and other relevant evidence was obtained from the reference lists of the articles identified, from the personal files of the authors and through contacts with experts. The articles were reviewed, classified according to study design and graded according to level of evidence. In addition, a systematic review of all published randomized controlled trials relating to dietary salt intake and hypertension was conducted. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: For normotensive people, a marked change in sodium intake is required to achieve a modest reduction in blood pressure (there is a decrease of 1 mm Hg in systolic blood pressure for every 100 mmol decrease in daily sodium intake). For hypertensive patients, the effects of dietary salt restriction are most pronounced if age is greater than 44 years. A decrease of 6.3 mm Hg in systolic blood pressure and 2.2 mm Hg in diastolic blood pressure per 100 mmol decrease in daily sodium intake was observed in people of this age group. For hypertensive patients 44 years of age and younger, the decreases were 2.4 mm Hg for systolic blood pressure and negligible for diastolic blood pressure. A diet in which salt is moderately restricted appears not to be associated with health risks. RECOMMENDATIONS: (1) Restriction of salt intake for the normotensive population is not recommended at present, because of insufficient evidence demonstrating that this would lead to a reduced incidence of hypertension. (2) To avoid excessive intake of salt, people should be counselled to choose foods low in salt (e.g., fresh fruits and vegetables), to avoid foods high in salt (e.g., pre-prepared foods), to refrain from adding salt at the table and minimize the amount of salt used in cooking, and to increase awareness of the salt content of food choices in restaurants. (3) For hypertensive patients, particularly those over the age of 44 years, it is recommended that the intake of dietary sodium be moderately restricted, to a target range of 90-130 mmol per day (which corresponds to 3-7 g of salt per day). (4) The salt consumption of hypertensive patients should be determined by interview. VALIDATION: These recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth International Conference on Preventive Cardiology. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at Health Canada, and the Heart and Stroke Foundation of Canada.     

Long term reduction in sodium balance: possible additional mechanism whereby nifedipine lowers blood pressure.

OBJECTIVE--To assess the changes in sodium excretion and sodium balance after withdrawal of long term nifedipine. DESIGN--Single blind, placebo controlled study in patients receiving fixed sodium and potassium intakes. SETTING--Blood pressure unit of a teaching hospital in south London. PATIENTS--Eight patients with mild to moderate uncomplicated essential hypertension who had been taking nifedipine 20 mg twice daily for at least six weeks. INTERVENTIONS--Withdrawal of nifedipine and replacement with matching placebo for one week. MAIN OUTCOME MEASURES--Urinary sodium excretion and cumulative sodium balance, body weight, plasma atrial natriuretic peptide concentrations, plasma renin activity and aldosterone concentrations, and blood pressure. RESULTS--During nifedipine withdrawal there was a significant reduction in urinary sodium excretion (day 1: -62.7 mmol/24 h; 95% confidence interval -90.3 to -35.0) and each patient retained a mean of 146 (SEM 26) mmol sodium over the week of replacement with placebo. Body weight and plasma atrial natriuretic peptide concentrations increased during the placebo period and seemed to be associated with the amount of sodium retained. Systolic blood pressure rose from 157 (9) to 165 (9) mmHg (95% confidence interval of difference -7.1 to 22.1) when nifedipine was replaced with matching placebo, and the rise seemed to be related to the amount of sodium that was retained. CONCLUSIONS--Nifedipine causes a long term reduction in sodium balance in patients with essential hypertension. This long term effect may contribute to the mechanism whereby nifedipine lowers blood pressure.     

Influence of non-steroidal anti-inflammatory drugs on diuretic treatment of mild to moderate essential hypertension.

In an open triple crossover study in 10 patients with mild to moderate essential hypertension the influence was investigated of adding indomethacin 50 mg, naproxen 250 mg, or sulindac 200 mg, each twice daily for four weeks, to diuretic treatment with hydrochlorothiazide 50 mg a day. After two weeks'' treatment with indomethacin a slight increase in blood pressure was observed, whereas both sulindac and naproxen tended to enhance the antihypertensive effect of hydrochlorothiazide. After treatment for four weeks, however, the effects of all three drugs on blood pressure appeared to be blunted. Furthermore, body weight increased significantly during treatment with indomethacin but not during treatment with naproxen or sulindac. No significant changes were found for various biochemical variables, including concentrations of plasma electrolytes and serum creatinine and albumin, plasma renin activity, plasma aldosterone concentration, and 24 hour urinary excretion of sodium and potassium, with the exception, however, of an increase in plasma potassium concentration during treatment with indomethacin. These observations suggest that the interaction of indomethacin, naproxen, and sulindac with diuretic treatment in mild to moderate essential hypertension is transient and of minor clinical importance.     

Water, cations, and norepinephrine content of cardiovascular tissues of unilaterally nephrectomized dogs treated with deoxycorticosterone and NaCl.

Deoxycorticosterone pivalate (2.5 mg/kg) given intramuscularly on four occasions 10-15 days apart over a period of 45 days to unilaterally nephrectomized adult male mongrel dogs, receiving as drinking solution 0.9% NaCl in 5% dextrose, resulted in an average sustained rise in the mean arterial blood pressure of 30 mm Hg (1 mm Hg - 133 N/m2) in 60% of the animals. Hypertensive dogs had in their arterial tissues generally more sodium, potassium, magnesium, and calcium than the similarly treated but non-hypertensive dogs, but compared to the tissues of operated untreated or unoperated normotensive dogs, only sodium and calcium were significantly higher. The dogs who were similarly treated but did not develop hypertension had in their arterial tissues less sodium, potassium, and magnesium than operated untreated or unoperated normotensive dogs. Norepinephrine content in the branches of mesenteric arteries of all deoxycorticosterone- and NaCl-treated animals, irrespective of their blood pressure, was significantly lower, and in the myocardium significantly higher, than either the unoperated normotensive or operated but not further treated dogs. It is concluded, therefore, that in deoxycorticosterone + NaCl treatment the dogs which developed hypertension had more arterial sodium, potassium, magnesium, and calcium than those who were similarly treated but remained within the limits of normal blood pressure, and that there was no difference between hypertensive and non-hypertensive dogs in regard to their cardiovascular norepinephrine content.     

Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations. Intersalt Cooperative Research Group.

OBJECTIVES--To assess further the relation in Intersalt of 24 hour urinary sodium to blood pressure of individuals and populations, and the difference in blood pressure from young adulthood into middle age. DESIGN--Standardised cross sectional study within and across populations. SETTING--52 population samples in 32 countries. SUBJECTS--10,074 men and women aged 20-59. MAIN OUTCOME MEASURES--Association of sodium and blood pressure from within population and cross population multiple linear regression analyses with multivariate correction for regression dilution bias. Relation of sample median daily urinary sodium excretion to difference in blood pressure with age. RESULTS--In within population analyses (n = 10,074), individual 24 hour urinary sodium excretion higher by 100 mmol (for example, 170 v 70 mmol) was associated with systolic/diastolic blood pressure higher on average by 3/0 to 6/3 mm Hg (with and without body mass in analyses). Associations were larger at ages 40-59. In cross population analyses (n = 52), sample median 24 hour sodium excretion higher by 100 mmol was associated with median systolic/diastolic pressure higher on average by 5-7/2-4 mm Hg, and estimated mean difference in systolic/diastolic pressure at age 55 compared with age 25 greater by 10-11/6 mm Hg. CONCLUSIONS--The strong, positive association of urinary sodium with systolic pressure of individuals concurs with Intersalt cross population findings and results of other studies. Higher urinary sodium is also associated with substantially greater differences in blood pressure in middle age compared with young adulthood. These results support recommendations for reduction of high salt intake in populations for prevention and control of adverse blood pressure levels.     

Nutritional management of hypertension: past, present, and future

A succinct overview of the nutritional management of hypertension, past, present, and future is presented. Prior to 1945, the low sodium diet and the rice-fruit diet were shown to be effective in reducing the blood pressure to normal levels in 35-40% of hypertensive patients. Between 1945 and the present, many studies were made on the effects of alcohol, water hardness, obesity, moderate restriction of sodium with increased potassium intake, increased dietary calcium, low animal and high unsaturated fat intake, and increased amounts of fiber in the diet. Criticisms are made of the very small magnitude, even if statistically significant, of blood pressure decreases and the too-short control periods in many instances, and also concerning the assumption of use of 24-h urinary sodium as an accurate index of the sodium intake, and of urinary creatinine as a physiological reference standard against the excretion of sodium. The author mentions, for possible future research, long-term studies of the effects of diets moderately restricted in sodium and high in potassium, of reducing weight and increasing physical activity in obese hypertensives, and of low animal and high polyunsaturated fat diets in patients with mild essential hypertension.