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In the presence of aldosterone, plasma sodium in the high physiological range stiffens endothelial cells and reduces the release of nitric oxide. We now demonstrate effects of extracellular potassium on stiffness of individual cultured bovine aortic endothelial cells by using the tip of an atomic force microscope as a mechanical nanosensor. An acute increase of potassium in the physiological range swells and softens the endothelial cell and increases the release of nitric oxide. A high physiological sodium concentration, in the presence of aldosterone, prevents these changes. We propose that the potassium effects are caused by submembranous cortical fluidization because cortical actin depolymerization induced by cytochalasin D mimics the effect of high potassium. In contrast, a low dose of trypsin, known to activate sodium influx through epithelial sodium channels, stiffens the submembranous cell cortex. Obviously, the cortical actin cytoskeleton switches from gelation to solation depending on the ambient sodium and potassium concentrations, whereas the center of the cell is not involved. Such a mechanism would control endothelial deformability and nitric oxide release, and thus influence systemic blood pressure.

Type II Bartter's syndrome is a hereditary hypokalemic renal salt-wasting disorder caused by mutations in the ROMK channel (Kir1.1; Kcnj1), mediating potassium recycling in the thick ascending limb of Henle's loop (TAL) and potassium secretion in the distal tubule and cortical collecting duct (CCT). Newborns with Type II Bartter are transiently hyperkalemic, consistent with loss of ROMK channel function in potassium secretion in distal convoluted tubule and CCT. Yet, these infants rapidly develop persistent hypokalemia owing to increased renal potassium excretion mediated by unknown mechanisms. Here, we used free-flow micropuncture and stationary microperfusion of the late distal tubule to explore the mechanism of renal potassium wasting in the Romk-deficient, Type II Bartter's mouse. We show that potassium absorption in the loop of Henle is reduced in Romk-deficient mice and can account for a significant fraction of renal potassium loss. In addition, we show that iberiotoxin (IBTX)-sensitive, flow-stimulated maxi-K channels account for sustained potassium secretion in the late distal tubule, despite loss of ROMK function. IBTX-sensitive potassium secretion is also increased in high-potassium-adapted wild-type mice. Thus, renal potassium wasting in Type II Bartter is due to both reduced reabsorption in the TAL and K secretion by max-K channels in the late distal tubule.

1. The possible natriuretic and kaliuretic effects of a single dose of lithium, as used in lithium clearance studies, were investigated in 15 healthy subjects on fixed sodium (100 mmol/24 h) and potassium (70 mmol/24 h) intakes. Lithium carbonate (300 mg or 600 mg) or placebo tablets were administered, double-blind and in random order, midway through a 48 h urine collection (divided into six 8 h periods), at 23.00 hours. 2. During the three 24 h periods which preceded the administration of lithium or placebo (control days), rates of sodium and potassium excretion followed normal circadian patterns, but no differences in excretion rates between the 3 control days were observed. Placebo tablets did not affect excretion rates. 3. After the 300 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 17 mmol (P less than 0.05); almost all of the natriuretic effect occurred during the first two 8 h periods. No effect on potassium excretion was observed. 4. After the 600 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 48 mmol (P less than 0.001) and 24 h potassium excretion increased by approximately 19 mmol (P less than 0.01). These effects were confined to the first two 8 h periods and thus occurred before and during the usual lithium clearance period. 5. Plasma renin activity, measured in 10 subjects, increased after the 600 mg dose of lithium carbonate (P less than 0.005), but plasma concentrations of aldosterone and atrial natriuretic peptide were not significantly affected. Neither the 300 mg dose of lithium carbonate nor the placebo tablets affected hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Both epidemiologic and clinical studies have suggested that an increase in potassium intake may lower blood pressure. However, the results of prospective clinical trials looking at the effect of oral potassium supplements on blood pressure have yielded conflicting results. For this reason, we reviewed 19 clinical trials examining the same end-point and involving a total of 586 participants (412 of whom had essential hypertension). Overall, the results of the trials indicate that oral potassium supplements significantly lower systolic blood pressure [-5.9 mmHg, -6.6 to -5.2 mmHg (mean, 95% confidence interval)] and diastolic blood pressure (-3.4 mmHg, -4.0 to 2.8 mmHg). The magnitude of the blood pressure lowering effect is greater in patients with high blood pressure (-8.2 mmHg, -9.1 to -7.3 mmHg for systolic and -4.5 mmHg, -5.2 to -3.8 mmHg for diastolic blood pressure) and appears to be more pronounced the longer the duration of the supplementation (P less than 0.05 and P less than 0.01 for systolic and diastolic, respectively). Based on this analysis, an increase in potassium intake should be included in the recommendations for a non-pharmacological approach to the control of blood pressure in uncomplicated essential hypertension.

The effects of alterations in dietary potassium (40, 80 and 160 mmol day-1) on endocrine status and on renal lithium clearance were assessed in 10 healthy subjects on a fixed sodium intake; measurements were made on the fifth day of each dietary regimen. Plasma aldosterone concentration was found to increase with potassium intake, whereas plasma renin activity and the plasma concentration of atrial natriuretic peptide did not change significantly. Neither absolute lithium clearance nor fractional lithium excretion was affected measurably by changes in dietary potassium, suggesting that provided the potassium intake remains within the normal range it is unnecessary to control this factor during lithium clearance studies in man.

The acute effects on urinary electrolyte excretion and plasma potassium were compared of the anti-hypertensive dihydrofuropyridine cicletanine with the thiazide bendrofluazide in 6 patients with uncomplicated essential hypertension. Cicletanine 50 mg or 100 mg and bendrofluazide 5 mg caused no acute decrease in blood pressure compared to placebo for 24 h after treatment. In the 24 h after a single dose of cicletanine 50 mg there was no increase in urinary sodium, potassium or volume compared to placebo. After a single dose of cicletanine 100 mg there was a significant increase in 2 h urinary sodium excretion compared to cicletanine 50 mg and in the first 6 h a significant increase in urinary potassium compared to placebo. Urine volume did not change significantly. After bendrofluazide 5 mg urinary sodium excretion increased significantly in the first 6 h as well as in the subsequent 18 h compared to placebo and both cicletanine 50 mg and 100 mg. Urinary potassium excretion was also significantly increased in the first 6 h after bendrofluazide compared to placebo, and urine volume significantly increased from 6 to 24 h after bendrofluazide 5 mg compared to placebo and cicletanine 100 mg. Plasma potassium was significantly reduced and plasma renin activity significantly increased 24 h after bendrofluazide 5 mg but these measurements were not significantly different from placebo after cicletanine 50 or 100 mg. These results suggest that cicletanine 100 mg has milder acute natriuretic effects than the thiazide bendrofluazide 5 mg. In contrast cicletanine 50 mg is associated with no major acute renal effects.(ABSTRACT TRUNCATED AT 250 WORDS)

There is increasing circumstantial evidence that the very high sodium diet combined with low potassium intake that most Western communities now eat may be, at least in part, responsible for the prevalence of high blood pressure. This circumstantial evidence combined with animal evidence has been considered sufficient in some countries to make a general recommendation to reduce sodium intake. If high sodium intake is an important cause of high blood pressure, it is not clear at the present time how it may do so. In this report, evidence is reviewed for one hypothesis suggesting an inherited defect in the kidney's ability to excrete sodium in patients who are going to develop essential hypertension, together with evidence for a raised concentration of an inhibitor of sodium transport. In patients with established hypertension, moderate restriction of sodium intake appears to lower blood pressure and moderate potassium supplementation to also lower blood pressure. While further evidence is required, particularly long-term studies, it would seem prudent to recommend to patients with essential hypertension or a strong family history of hypertension that they restrict dietary sodium intake moderately and increase dietary potassium intake by the consumption of more fruits and vegetables and, perhaps, the use of a potassium-based salt substitute. This regimen could obviate or reduce the need for drug treatment in some patients with mild to moderate hypertension.

The effects of synthetic human and rat atrial peptides on sodium and potassium ion transport has been investigated in intact human erythrocytes. The effects of these peptides have been tested on the active, sodium pump-dependent (ouabain-sensitive) and on the sodium-potassium cotransport system (bumetanide-sensitive) with 86Rb used as a tracer. Human (alpha-ANP, 28 amino acids) or rat (atriopeptin III) atrial peptides, over a wide range of concentrations, did not influence the uptake of 86Rb in either the ouabain-sensitive or the bumetanide-sensitive transport system. These results suggest that the natriuretic effect of the atrial peptides is not mediated through inhibition of the sodium pump or the loop-diuretic-sensitive Na-K cotransport.

1 The blood pressure lowering effect of xipamide, a non-thiazide diuretic given for 6 weeks was compared in a randomised cross-over trial with that of cyclopenthiazide in 14 patients with essential hypertension. 2 Xipamide 10 or 20 mg given once daily was as effective in lowering supine blood pressure as daily cyclopenthiazide 0.5 mg. There was no difference in the blood pressure lowering effect of 10 mg xipamide daily for 2 weeks compared to 20 mg daily given for a further 4 weeks. 3 Plasma potassium was reduced by both drugs, but markedly more after both 10 mg and 20 mg xipamide than after cyclopenthiazide 0.5 mg. By the sixth week of treatment 13 of 14 patients on xipamide but only 6 of 14 on cyclopenthiazide has plasma potassium concentrations of, or less than, 3.5 mmol/l. The fall in plasma potassium was significantly greater and the final plasma potassium concentration was significantly lower after either dose of xipamide than after cyclopenthiazide. 4 These results suggest that 10 mg or 20 mg of xipamide daily is effective in lowering blood pressure in hypertensive patients but is associated with hypokalaemia. In view of recent evidence linking diuretic-induced hypokalaemia with cardiac dysrhythmias in patients with essential hypertension we would suggest that thiazide diuretics be used in preference to xipamide for the routine management of essential hypertension. Our results also suggest that the currently recommended dose of xipamide (20 mg) for the treatment of hypertension is excessive, and lower amounts than 10 mg per day might possibly be as effective in lowering blood pressure with less adverse metabolic consequences.

Twenty-three unselected patients with mild to moderate essential hypertension whose average supine blood pressure after 2 months of observation on no treatment was 154/99 mm Hg were entered into an 8-week double-blind randomised crossover study of 1 month's treatment with slow release potassium tablets (64 mmol/day) versus placebo without alteration of dietary sodium or potassium intake. By the fourth week mean supine blood pressure had fallen by 4% with potassium supplementation compared with placebo. In a separate metabolic study the effect of 12 slow release potassium tablets (98 mmol/day) was studied in 12 patients with mild essential hypertension who had a fixed sodium and potassium intake. The increase in potassium intake caused immediate natriuresis with an average cumulative sodium loss of 110 mmol per patient. In spite of this loss of sodium there was no rise in plasma renin activity, but there was a significant increase in plasma noradrenaline level. On an average western diet containing approximately 150 mmol of sodium/day, potassium chloride supplementation causes a small but worthwhile fall in blood pressure in many patients with essential hypertension. It is likely that part of the mechanism of this fall in blood pressure is related to the increase in potassium intake causing a loss of sodium with no compensatory rise in renin release.

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.

Much circumstantial and some direct evidence links a high sodium, low potassium intake to the development of essential hypertension. However, studies to prove a definite causative relationship in man are unlikely to be done for the practical reason that they need to be carried out over a whole generation. Restriction of sodium intake does lower blood pressure in many hypertensive subjects. This fall appears to be mediated in part by a diminished renin response to the sodium restriction as blood pressure becomes more severe. Less substantive evidence also suggests that increasing potassium intake may lower blood pressure but this effect seems to be more apparent when both animals and man are on a high sodium intake. It would seem sensible, therefore, in the light of present knowledge, to advise communities that have a high sodium, low potassium diet they they may benefit from a reduction in sodium and an increase in potassium intake. Patients who are already known to have high blood pressure should be advised to reduce sodium intake along with other non-pharmacological advice. In some patients this will be sufficient to control the blood pressure. In others who may then require drug treatment, the blood pressure lowering effect of beta-blockers and converting enzyme inhibitors will be enhanced by the sodium restriction.

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.

To study the relationship between salt intake and blood pressure in children and adolescents, we analysed the data of a large cross-sectional study (the National Diet and Nutrition Survey for young people), which was carried out in Great Britain in 1997 in a nationally representative sample of children aged between 4 and 18 years. A total of 1658 participants had both salt intake and blood pressure recorded. Salt intake was assessed by a 7-day dietary record. The average salt intake, which did not include salt added in cooking or at the table, was 4.7±0.2 g/day at the age of 4 years. With increasing age, there was an increase in salt intake, and by the age of 18 years, salt intake was 6.8±0.2 g/day. There was a significant association of salt intake with systolic blood pressure as well as with pulse pressure after adjusting for age, sex, body mass index and dietary potassium intake. An increase of 1 g/day in salt intake was related to an increase of 0.4 mm Hg in systolic and 0.6 mm Hg in pulse pressure. The magnitude of the association with systolic blood pressure is very similar to that observed in a recent meta-analysis of controlled trials where salt intake was reduced. The consistent finding of our present analysis of a random sample of free-living individuals with that from controlled salt reduction trials provides further support for a reduction in salt intake in children and adolescents.Journal of Human Hypertension (2008) 22, 4–11; doi:10.1038/sj.jhh.1002268; published online 6 September 2007 [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death and disability world-wide. Blood pressure, throughout the range seen in developed countries, is the most important risk factor for cardiovascular disease. Lowering blood pressure within the whole population by lifestyle interventions, such as reducing dietary salt intake and increasing the consumption of fruit and vegetables, will be of great benefit. Blood pressure-lowering trials also demonstrate immense benefits in preventing strokes, heart failure and coronary heart disease. There are no differences in outcome between the different methods used to lower blood pressure and the benefit is proportional to the degree of blood pressure-lowering. Thiazide diuretics are effective in lowering blood pressure and have been the most widely prescribed blood pressure-lowering drugs. They work by causing both sodium and water loss, but also cause potassium loss and a fall in plasma potassium levels. The latter may mitigate the beneficial effects from blood pressure-lowering. Some diuretics, such as spironolactone, affect the distal tubule and do not cause a fall in plasma potassium levels. However, spironolactone has endocrine side-effects associated with the fact that it is not specific for the mineralocorticoid receptor. The development of a more selective aldosterone antagonist without endocrine side-effects could be a major advance as it would be able to oppose the effects of aldosterone, both on sodium retention and potassium loss and the other vascular effects. [ABSTRACT FROM AUTHOR]