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Background: Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation., Methods: In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive (48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel beta subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing., Findings: 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normotensive participants possessed the T594M variant (odds ratio [OR]=4.17 [95% CI 1.12-18.25], p=0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2% hypertensive, 57.7% normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR=5.52 [1.40-30.61], p=0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median=0.19 ng mL(-1) h(-1)) than in 39 untreated hypertensive individuals without the variant (median=0.45 ng mL(-1) h(-1), p=0.009)., Interpretation: Among black London people the T594M sodium-channel beta subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.

Background: Stroke is directly related to blood pressure and treatment trials in older hypertensive individuals show a reduction in strokes. However, the majority of strokes occur in normotensive individuals in whom no attempt is made to lower blood pressure. We compared the effects of modest salt restriction on blood pressure in older hypertensive and normotensive people., Methods: 47 untreated elderly people (24 men, age range 60-78 years; blood-pressure range 123-205 mm Hg systolic and 64-112 mm Hg diastolic) completed a 2-month double-blind randomised placebo-controlled crossover study of modest salt restriction with slow sodium and placebo to give a salt intake of either 10 g (equivalent to the normal amount for the UK population) or 5 g., Findings: On the normal salt intake for the UK population, supine blood pressure was 163/90 (SD 21/10) mm Hg with urinary sodium excretion of 177 (49) mmol/day. With modest sodium restriction, blood pressure fell to 156/87 (22/9) mm Hg (p < 0.001/0.004) with a urinary sodium excretion of 94 (50) mmol/day. A reduction in sodium intake of 83 mmol/day was associated with a reduction of 7.2/3.2 mm Hg. There was no significant difference in the blood-pressure fall between 18 normotensive and 29 hypertensive participants (8.2/3.9 vs 6.6/2.7 mm Hg)., Interpretation: A modest reduction in salt intake leads to a fall in blood pressure in both normotensive and hypertensive older people similar to that in outcome trials of thiazide-based treatment. Since the majority of strokes in older people occur below the current definition of hypertension, our results have important implications for the prevention of stroke.

Diuretics are now commonly prescribed for women with so-called idiopathic oedema. Two patients with idiopathic oedema, one of whom was oedematous on diuretics, had the diuretics stopped. In one the oedema became much worse, and in the other oedema developed. However, this oedema disappeared spontaneously in both patients and they have remained free of oedema on no treatment. It is suggested that in some patients treated with diuretics compensatory mechanisms to retain sodium and water may be stronger than the diuretic-effect itself and may lead to perpetuation of unnecessary treatment.

20 patients with mild hypertension (average supine blood pressure without treatment, 164/101 mm Hg) reduced their salt intake to 50 mmol (3 g) per day for a month. They then entered a 3 month double-blind randomised crossover study of three levels of sodium intake: 200, 100, and 50 mmol per day. Blood pressure was significantly reduced on the middle and lowest sodium intakes. The average fall in blood pressure from the highest to the lowest sodium intake was 16/9 mm Hg. Patients continued to restrict their sodium intake for a further year. In 16 of the 20 patients blood pressure remained well controlled with salt restriction alone. Supine blood pressure at 1 year was 142/87 (SE 3/2) mm Hg with a 24 h urinary sodium excretion of 54 (7) mmol. These results show a progressive blood pressure fall as salt intake is reduced and that, in many patients with mild essential hypertension, blood pressure can be controlled without the need for drug therapy.

23 unselected patients with mild to moderate essential hypertension, whose average supine blood pressure after two months' observation on no treatment was 154/99 mm Hg, were entered into an eight week double blind randomised crossover study of one month's treatment with slow release potassium tablets (60 mmol/day) versus placebo without alteration of dietary sodium or potassium intake. By the fourth week mean supine blood pressure had fallen by 4% on potassium supplementation compared with placebo. Urinary potassium excretion increased from 62 +/- 4.7 mmol/24 h on placebo to 118 +/- 7.4 mmol/24 h on potassium. The fall in blood pressure was not related to urinary sodium excretion before entry to the trial or while on placebo. Moderate potassium supplementation caused a small but significant fall in blood pressure in patients with mild to moderate essential hypertension and could be additive to the effects of moderate sodium restriction. This increase in potassium intake could be achieved with a potassium-based salt substitute and a moderate increase in vegetable and fruit consumption. Moderate dietary sodium restriction with dietary potassium supplementation may obviate or reduce the need for drug treatment in some patients with mild to moderate hypertension.

Ten women with "idiopathic" edema had sodium and water retention and a rapid gain in weight when their accustomed intake of diuretics was suddenly stopped. The magnitude of these changes was directly related to the levels of plasma-rening activity before withdrawal of diuretics. Nine patients became edematous. Within 10 days of stopping diuretics, plasma-renin activity and urinary aldosterone excretion decreased to normal or below and within 20 days weight-gain and edema had subsided in seven patients. But the greatest gains in weight, in three patients, were sustained beyond 20 days. Nevertheless, a year later, two of these three patients were free of edema without the use of diuretics. Intermittent edema of unknown cause in most, if not all, otherwise healthy women seems to result from their use of diuretics, abetted in some patients by self-imposed flucuation of sodium and carbohydrate intake, and does not appear to be idiopathic.

Plasma levels of immunoreactive atrial natriuretic peptide (IrANP) were measured in healthy normotensive subjects before and after saline infusion and changes in dietary salt intakes. When 2 litres of 0.9% saline (308 mmol Na+) were infused over 1 h, plasma levels (mean +/- SD) of IrANP increased from 5.8 +/- 2.8 pg/ml to 15.8 +/- 12.5 pg/ml. Plasma levels on the fifth day of a low sodium diet (10 mmol/day) were 3.8 +/- 2.4 pg/ml, a normal sodium intake (150 mmol/day) 6.4 +/- 2.9 pg/ml, and a high salt intake (350 mmol/day) 12.7 +/- 6 pg/ml. These results suggest that atrial natriuretic peptides could be important hormones in the control of sodium balance in normal man.

Plasma levels (mean +/- SD) of immunoreactive atrial natriuretic peptides (ANP) were significantly higher in 28 hypertensive subjects (17.1 +/- 13.8 pg/ml) than in 24 normotensive subjects (8.4 +/- 3.7 pg/ml) matched as far as possible for age, sex, and race. All subjects were studied on their normal dietary sodium intake. In the normotensive subjects ANP levels were significantly correlated with age but not with blood pressure, whereas in the hypertensive subjects ANP levels were significantly correlated with systolic blood pressure but not with age. These findings may indicate a compensatory reaction to a diminished renal capacity for sodium excretion, in response to increasing age in normotensive subjects and to higher blood pressure in hypertensive subjects.

8 of 16 patients with nephrotic syndrome had normal or low plasma renin activity while spontaneously retaining sodium. The other 8 patients had a high plasma renin activity which may have caused the sodium retention. Oral captopril and albumin infusion given separately both suppressed the renin system in these patients. Despite this, urinary sodium excretion remained less than sodium intake and patients continued to retain sodium and gain weight. These results suggest that, even in patients with nephrotic syndrome who do have stimulation of the renin angiotensin system, some other overriding mechanism is responsible for sodium retention. Therefore it seems unlikely that angiotensin-converting enzyme inhibitors will be useful in the treatment of sodium retention in nephrotic syndrome.

Twenty patients with chronic renal failure and either urinary or respiratory tract infection were treated with co-trimoxazole. Seventeen patients showed no deterioration in renal function while receiving co-trimoxazole. Deterioration in renal function during treatment in the other three patients was due to factors other than administration of the drug. It is concluded that co-trimoxazole can be used in patients with chronic renal failure provided the dose is adjusted according to the degree of renal failure.

Nineteen unselected patients with mild to moderate essential hypertension, whose average supine blood pressure after two months' observation on no treatment was 156/98 mm Hg, were advised not to add salt to food and to avoid sodium-laden foods. After 2 weeks of sodium restriction patients were entered into an 8-week double-blind randomised crossover study of 'Slow Sodium' (Ciba) versus slow sodium placebo. The mean supine blood pressure was 7.1 mm Hg (6.1%) lower in the fourth week of placebo than that in the fourth week of slow sodium (p less than 0.001). Urinary sodium excretion in the fourth week of slow sodium was 162 +/- 9 mmol/24 h and that in the fourth week of placebo was 86 mmol +/- 9 mmol/24 h (p less than 0.001). There was no difference in potassium excretion. These results suggest that moderate sodium restriction achieved by not adding salt and avoiding sodium-laden foods should, if not already, become part of the management of essential hypertension.

Ten patients with Addison's disease, nine with undetectable plasma aldosterone, were found to be sodium and water depleted with high levels of plasma-renin activity despite receiving 0.05-0.1 mg/day of fludrocortisone and optimum doses of glucocorticoid replacement therapy. Fludrocortisone was withdrawn while patients were in hospital on a fixed sodium intake. There was an immediate natriuresis with a further increase in plasma-renin activity. When a daily dose of 0.3 mg of fludrocortisone was given all patients retained sodium and water and gained weight. There was a fall in plasma-renin activity in all patients and an associated fall in blood urea and plasma potassium, and an increase in plasma volume; oedema developed in some patients. At outpatient follow-up, the dose of fludrocortisone was adjusted according to plasma-renin activity. Most patients required 0.2 mg of fludrocortisone to maintain adequate sodium and water balance. These results suggest that patients with Addison's disease on 0.05-0.1 mg of fludrocortisone with undetectable plasma aldosterone levels are currently being undertreated with fludrocortisone. The best way of assessing sodium balance in these patients and their response to fludrocortisone is by measurement of plasma-renin activity in conjunction with 24 h urinary sodium excretion.