Dietary Potassium Supplementation Research Articles

Genetic variants in the ADD1 and GNB3 genes and blood pressure response to potassium supplementation

Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes. However, blood pressure (BP) responses to potassium supplementation vary among individuals. This study was designed to examine the association between 12 single nucleotide polymorphisms (SNPs) in the adducin 1 alpha (ADD1) and guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) genes and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) responses to potassium-supplementation. We conducted a 7-day high-sodium intervention (307.8 mmol sodium/day) followed by a 7-day high-sodium with potassium-supplementation (60 mmol potassium/day) among 1906 Han Chinese participants from rural north China. BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer. We identified significant associations between ADD1 variant rs17833172 and SBP, DBP, and MAP responses to potassium-supplementation (all P < 0.0001) that remained significant after adjustment for multiple comparisons. In participants that were heterozygous or homozygous for the G allele of this marker, SBP, DBP, and MAP response to potassium-supplementation were − 3.52 ( − 3.82, − 3.21), − 1.41 ( − 1.66, − 1.15) and − 2.12 ( − 2.37, − 1.87), respectively, as compared to the corresponding responses of 1.99 (0.25, 3.73), − 0.65 ( − 0.10, − 0.21), and − 0.23 ( − 0.37, 0.83), respectively, for those who were homozygous for A allele. In addition, participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation (P = 0.0041 and 0.01, respectively), which was also significant after correction for multiple testing. DBP and MAP responses to potassium-supplementation were − 1.36 ( − 1.63, − 1.10) and − 2.07 ( − 2.32, − 1.82) for those with at least G allele compared to corresponding responses of 0.86 ( − 0.68, 2.40) and − 0.45 ( − 1.74, 0.84) for those who were homozygous for A allele. In summary, our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation, which could have important clinical and public health implications. Future studies aimed at replicating these novel findings are warranted.

Protective Effect of Dietary Potassium against Cardiovascular Damage in Salt-Sensitive Hypertension: Possible Role of its Antioxidant Action

It is well known that high salt intake induces hypertension and cardiovascular damage, while dietary potassium supplementation counteracts these harmful effects. Actually, the protective effect of potassium is strengthened with excess salt as compared with salt depletion. Although the precise mechanisms have not been fully elucidated, in our previous reports, the antihypertensive effect of dietary potassium was accompanied by sympathetic nerve inhibition in salt-sensitive hypertension. Also, potassium supplement suppressed salt-induced insulin resistance. These effects of dietary potassium can explain its cardio- and vasculo-protective action in addition to the potassium supplementation induced decreased salt-induced rise in blood pressure. On the other hand, salt-sensitive hypertension is associated with reactive oxygen species (ROS) overproduction. Moreover, sympathoexcitation can be induced by central ROS upregulation and insulin resistance can be caused by ROS excess in the target organs of insulin, such as skeletal muscle. Conversely, the seemingly different actions of potassium can be explained by the antioxidant effect of dietary potassium; in our recent studies, potassium supplementation inhibits salt-induced progress of cardiac diastolic dysfunction and vascular neointima formation by cuff placement around arteries, associated with the inhibition of regional ROS overproduction, in salt-sensitive hypertension. Thus, it is possible that dietary potassium protects against salt-induced cardiovascular damage by the reduction of ROS generation and by central sympatholytic action and amelioration of insulin resistance induced through its antioxidant effect.

Correlation Between Blood Pressure Responses to Dietary Sodium and Potassium Intervention in a Chinese Population

Blood pressure (BP) responses to dietary sodium and potassium intake vary among individuals. We examined the correlation between BP responses to dietary low-sodium, high-sodium, and potassium supplementation interventions in a feeding study. A total of 1,906 Chinese aged > or = 16 years participated in the dietary intervention that included a 7-day low-salt intervention (51.3 mmol/day), a 7-day high-salt intervention (307.8 mmol/day), and a 7-day high-salt plus potassium supplementation (60 mmol/day) intervention. BP was measured nine times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer. The correlation coefficients (95% confidence intervals (CIs)) of the BP responses to low-sodium and high-sodium interventions were -0.47 (-0.51 to -0.44), -0.47 (-0.50 to -0.43), and -0.45 (-0.49 to -0.42) for systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP), respectively (all P < 0.0001). The correlation coefficients (95% CI) of the BP responses to high-sodium intervention and potassium supplementation were -0.52 (-0.56 to -0.49), -0.48 (-0.52 to 0.45), and -0.52 (-0.55 to -0.48) for SBP, DBP, and MAP, respectively (all P < 0.0001). The kappa coefficients were moderate, varying from 0.28 to 0.34, between BP responses to low-sodium and high-sodium interventions (all P < 0.0001). These results indicate there is a moderate correlation between BP responses to low-sodium and to high-sodium interventions, and BP responses to high-sodium intervention and potassium supplementation. Furthermore, our study suggests that individuals who were more sensitive to high-sodium diet might benefit more from a low-sodium and/or high-potassium intervention aimed at lowering BP levels.

Mesures adjuvantes à une corticothérapie systémique prolongée : description des pratiques des médecins internistes français

IntroductionExcept for the prevention of osteoporosis, no consensual recommendations are available regarding the therapeutic measures associated with the prescription of long-term corticosteroid therapy. The aim of this study was to assess the internal medicine physicians’ practices regarding the prescription of long-term corticosteroid therapy. MethodsIn September 2007, we sent, by e-mail, a questionnaire to 813 internal medicine physicians, members of the French National Society of Internal Medicine. With this questionnaire, we assessed the frequency of prescription of measures sometimes associated with systemic corticosteroids and for whom no consensual recommendations were available (dietary advices, physical training, potassium supplementation, gastric protection, influenza vaccination and prescription of hydrocortisone). ResultsThree hundred and thirty-six out of 813 internal medicine physicians completed the questionnaire (response rate: 41%). The practitioners were predominantly male (71%) and mainly engaged in tertiary centres (53%). Regarding the dietary measures associated with the prescription of corticosteroids, low-sodium diet was recommended by most of the physicians, 69% of them prescribing such dietary regimen in more than 80% of their corticosteroid-treated patients. The concomitant prescription of caloric restriction, low-carbohydrate diet and/or high-protein diet was not consensual. The prescription of muscular physiotherapy was unusual, 74% of physicians prescribing such reeducation in less than 20% of their patients. The frequency of recommendation for daily physical training varied between physicians as well as for potassium supplementation, gastric protection, influenza vaccination or hydrocortisone prescription. ConclusionThere is no consensus between French internal medicine physicians regarding most of the measures, which must be prescribed in association with a long-term corticosteroid therapy.

Dietary potassium supplementation improves vascular structure and ameliorates the damage caused by cerebral ischemia in normotensive rats

BackgroundDietary potassium supplementation in hypertensive rats is cardioprotective. This protection includes a blood pressure independent reduction in the amount of damage caused by cerebral ischemia. Therefore, we hypothesized that dietary potassium supplementation would improve the outcome of ischemic stroke by improving cerebral vessel structure in normotensive rats.MethodsWistar Kyoto (WKY) rats were fed a high (HK) or low potassium (LK) diet for six weeks from six weeks of age. At the end of treatment, cerebral ischemia was induced by middle cerebral artery (MCA) occlusion and the resultant infarct was quantified and expressed as a percentage of the hemisphere infarcted (%HI). MCA structure was assessed in an additional group of rats using a pressurized arteriograph.ResultsThe cerebral infarct was significantly smaller in rats fed the HK diet, compared to rats fed the LK diet (21 ± 5.4 vs 33.5 ± 4.8 %HI HK vs LK p < 0.05). Vessel structure was improved in WKY rats fed the HK diet as indicated by an increase in the MCA lumen (298 ± 6.3 vs 276 ± 3.9 μm HK vs LK p < 0.05) and outer diameters (322 ± 7.6 vs 305 ± 4.8 μm HK vs LK p < 0.05). Wall thickness and area were unchanged, suggesting an outward euthrophic remodelling process. The HK diet had no effect on body weight or telemetry blood pressure.ConclusionThese studies are the first to show a beneficial effect of dietary potassium in rats with normal blood pressure.

Protective Effect of Dietary Potassium Against Vascular Injury in Salt-Sensitive Hypertension

Hypertensive cardiovascular damage is accelerated by salt loading but counteracted by dietary potassium supplementation. We suggested recently that antioxidant actions of potassium contribute to protection against salt-induced cardiac dysfunction. Therefore, we examined whether potassium supplementation ameliorated cuff-induced vascular injury in salt-sensitive hypertension via suppression of oxidative stress. Four-week-old Dahl salt-sensitive rats were fed a normal-salt (0.3% NaCl), high-salt (8% NaCl), or high-salt plus high-potassium (8% KCl) diet for 5 weeks, and some of the rats fed a high-salt diet were also given antioxidants. One week after the start of the treatments, a silicone cuff was implanted around the femoral artery. Examination revealed increased cuff-induced neointimal proliferation with adventitial macrophage infiltration in arteries from salt-loaded Dahl salt-sensitive rats compared with that in arteries from non-salt-loaded animals (intima/media ratio: 0.471+/-0.070 versus 0.302+/-0.037; P<0.05), associated with regional superoxide overproduction and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and mRNA overexpression. On the other hand, simultaneous potassium supplementation attenuated salt-induced neointimal hyperplasia (intima/media ratio: 0.205+/-0.012; P<0.001), adventitial macrophage infiltration, superoxide overproduction, and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and overexpression. Antioxidants, which decrease vascular oxidative stress, also reduced neointima formation induced by salt excess. In conclusion, high-potassium diets seems to have a protective effect against the development of vascular damage induced by salt loading mediated, at least in part, through suppression of the production of reactive oxygen species probably generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase.

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.

A high-potassium diet reduces infarct size and improves vascular structure in hypertensive rats

High-potassium diets can improve vascular function, yet the effects of potassium supplementation on ischemic stroke have not been studied. We hypothesized that dietary potassium supplementation would reduce ischemic cerebral infarct size by reversing cerebral artery hypertrophy. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed diets containing 0.79% potassium (LK) or 2.11% potassium (HK) for 6 wk; Wistar-Kyoto (WKY) rats were fed the LK diet. The HK diet did not reduce blood pressure, as measured by telemetry, in the SHRSP. Cerebral ischemia was induced by middle cerebral artery (MCA) occlusion. The resultant infarct was smaller in the HK-SHRSP than in the LK-SHRSP: 55.1 +/- 6.3 vs. 71.4 +/- 2.4% of the hemisphere infarcted (P < 0.05). Infarcts were smaller in WKY rats (33.5 +/- 4.8%) than in LK-SHRSP or HK-SHRSP. The vessel wall of MCAs from LK-SHRSP was hypertrophied compared with WKY rats; this was reversed in HK-SHRSP. RT-PCR analysis of the cerebral vessels showed that expression of platelet-derived growth factor receptors-alpha and -beta, epidermal growth factor receptor, and collagen I and III was increased in the vessels from LK-SHRSP compared with WKY rats and reduced in HK-SHRSP. These results suggest that potassium supplementation provides neuroprotection in a model of ischemic stroke independent of blood pressure and possibly through changes in vascular structure.

Potassium Supplementation Reduces Cardiac and Renal Hypertrophy Independent of Blood Pressure in DOCA/Salt Mice

We have demonstrated previously that deoxycorticosterone acetate (DOCA)/salt induces cardiac hypertrophy and left ventricular dysfunction independent of blood pressure (BP) in 1-renin gene mice. Because these mice also develop hypokalemia and metabolic alkalosis caused by mineralocorticoid excess, we investigated whether correcting hypokalemia by dietary potassium supplementation would prevent the DOCA/salt-induced cardiac hypertrophy, cardiac dysfunction, and electrocardiographic changes in normotensive, 1-renin gene and hypertensive, 2-renin gene mice. All mice were studied after 5 weeks of DOCA and salt administration. Potassium was given by adding 0.4 or 0.6% KCl to the drinking water. Our results show that correction of hypokalemia and metabolic alkalosis prevents cardiac hypertrophy and normalizes cardiac function without affecting BP in normotensive, 1-renin gene mice. In hypertensive, 2-renin gene mice, potassium supplementation induces a significant decrease in BP. The decrease in BP and correction of kalemia are associated with a significant but partial correction of cardiac hypertrophy. In both group of mice, electrocardiographic alterations were measured after administration of DOCA/salt, which could be corrected by potassium supplementation. Thus, these results show that correction of hypokalemia and metabolic alkalosis does prevent the development of cardiac hypertrophy and normalizes cardiac function independent of BP in normotensive, 1-renin gene mice that receive excess mineralocorticoid and salt. In 2-renin gene, hypertensive mice, potassium supplementation also prevents the development of cardiac hypertrophy, but the effect cannot be separated from the decrease in BP.

Role of Salt and Potassium in Hypertension and the Associated Organ Damages

Excessive salt intake is well-known to be one of the major environmental factor not only to develop human hypertension but also to induce cardiovascular damages. On the other hand, dietary potassium supplementation exerts both anti-hypertensive and cardiovascular protective effects in salt-induced hypertension. In the earlier studies including us, it was suggested that the anti-hypertensive mechanism of dietary potassium is natriuresis and sympatho-inhibitory action. Recently, it has been clarified that salt loading increases production of reactive oxygen species (ROS) in saltsensitive hypertension model animals. Because ROS overproduction induces several disadvantages, such as insulin resistance, the peripheral and central sympathetic overactivity, and an enhanced oxidized low density lipoprotein (LDL) receptor-1, lectin-like oxidized LDL receptor (LOX-1) expression, antioxidants may prevent salt-induced hypertension and cardiovascular damages. Interestingly, some investigators have demonstrated that potassium has antioxidant effect. Indeed, dietary potassium supplementation ameliorates insulin resistance, sympathetic overactivity and LOX-1 upregulation associated with decrement of ROS production. Thus, opposite actions between salt and potassium on ROS production may play an important role of their influences on blood pressure and cardiovascular effects.

Increased dietary sodium partially blunts the amelioration of insulin resistance induced by dietary potassium supplementation in a neuroendocrine model of visceral obesity

Increased dietary sodium partially blunts the amelioration of insulin resistance induced by dietary potassium supplementation in a neuroendocrine model of visceral obesity

Cardiac Damage Prevention by Eplerenone: Comparison With Low Sodium Diet or Potassium Loading

To determine the extent to which dietary sodium modulates aldosterone-induced cardiovascular damage, and to determine whether increased dietary potassium can prevent this damage, we used the Nomega-nitro-L-arginine methyl ester (L-NAME)/angiotensin II (Ang II) rat model of cardiac injury. This model is dependent on the presence of aldosterone for the occurrence of myocardial damage. Two sets of experiments were performed. In the first set, the following groups were studied: (1) 1% NaCl to drink (control group); (2) L-NAME/Ang II with water to drink (low salt group); (3) L-NAME/Ang II/1% NaCl (high salt group); (4) L-NAME/Ang II/1% NaCl/eplerenone (eplerenone group). Systolic blood pressure increased similarly in all groups compared with controls. Compared with the controls, the high salt group, but not the low salt or eplerenone groups, developed significant myocardial damage. In the second set of experiments three groups of animals were studied: (1) L-NAME/Ang II/1%NaCl (high salt group) (2) L-NAME/Ang II/1%NaCl/eplerenone (eplerenone group), and (3) L-NAME/Ang II/1%NaCl with an extra 1% KCl in food (high dietary potassium group). Eplerenone, but not dietary potassium supplementation, prevented the development of cardiac damage. Thus, mineralocorticoid receptor antagonist treatment and low sodium diet were effective in preventing cardiac damage, which suggests that a minimal level of aldosterone and a moderately high sodium diet are both required for the development of the cardiovascular damage in the L-NAME/Ang II model. The inability of potassium supplementation to reduce myocardial damage suggests that eplerenone's protective effect is not due to its potassium-sparing ability, but is rather related to some other feature of its selective aldosterone antagonism.

Dietary potassium requirement of juvenile grass shrimp Penaeus monodon

: A feeding trial was conducted to estimate the minimal dietary potassium (K) requirement for juvenile grass shrimp Penaeus monodon. Purified diets with seven levels (0, 0.3, 0.6, 0.9, 1.2, 1.5, 2.0 g/100 g) of supplemental potassium were fed to P. monodon (mean initial weight 0.75 ± 0.01 g) for 8 weeks. Each diet was fed to three replicate groups of shrimp. The rearing water contained 360 mg/L potassium. Weight gain and protein efficiency ratio (PER) of shrimp improved as dietary potassium supplementation level increased up to 1.5 g K/100 g diet and thereafter declined significantly (P < 0.05). Feed efficiency (FE) of shrimp also showed a similar trend. However, whole body K concentration of the shrimp kept an increasing trend up to 2.0 g K/100 g diet. Analysis of the weight gain (percent) and PER of the shrimp by polynomial regression indicate that the minimal dietary potassium requirement in growing P. monodon is approximately 1.2 g/100 g.

Dietary potassium and magnesium supplementation in cyclosporine-induced hypertension and nephrotoxicity

Cyclosporine A (CsA)-induced hypertension and nephrotoxicity are aggravated by high sodium intake. Accumulating evidence suggests that potassium and magnesium supplementation could protect against the detrimental effects of dietary salt. In the present study, we tested the hypothesis of whether concurrent supplementation with potassium and magnesium could protect against the development of CsA-induced hypertension and nephrotoxicity more effectively than supplementation with one mineral alone. Eight-week-old spontaneously hypertensive rats (SHRs) were divided into four groups (N = 10 in each group): (1) CsA group (5 mg/kg subcutaneously) receiving high-sodium diet (Na 2.6%, K 0.8%, Mg 0.2% wt/wt); (2) CsA group receiving a high-sodium, high-potassium diet (Na 2.6%, K 2.4%, Mg 0.2%); (3) CsA group receiving high-sodium, high-magnesium diet (Na 2.6%, K 0.8%, Mg 0.6%); and (4) CsA group receiving high-sodium, high-potassium, high-magnesium diet (Na 2.6%, K 2.4%, Mg 0.6%). CsA induced severe hypertension and deteriorated renal functions in SHRs on high-sodium diet. Histologically, the kidneys showed severe thickening of the media of the afferent artery with fibrinoid necrosis. Potassium supplementation lowered blood pressure (198 +/- 5 vs. 212 +/- 2 mm Hg, P < 0.05) and partially prevented the development of proteinuria (-25%, P < 0.05). Magnesium supplementation decreased blood pressure to the same extent but improved renal functions more effectively than potassium. The greatest protection against CsA toxicity was achieved when dietary potassium and magnesium supplementations were combined. Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion, a marker for renal proximal tubular damage, increased progressively in CsA-treated SHRs on the high-sodium diet. Neither potassium nor magnesium influenced urinary NAG excretion. We also estimated the activity of the renal dopaminergic system by measuring 24-hour urinary dopamine excretion rates. CsA suppressed the renal dopaminergic system during high-sodium diet. Magnesium supplementation, alone and in combination with potassium, protected against the development of renal dopaminergic deficiency in CsA-treated SHRs on high-sodium diet. Magnesium supplementation increased plasma-free ionized magnesium (iMg) and bone magnesium by 50 and 16%, respectively. Our findings indicate that both potassium and magnesium supplementations showed beneficial effects against CsA-induced hypertension and nephrotoxicity. The protective effect of magnesium clearly exceeded that of potassium. The greatest protection against CsA toxicity was achieved when potassium and magnesium were combined. We also provide evidence that the development of CsA-induced glomerular, tubular, and vascular lesions are associated with renal dopaminergic deficiency.

Effects of Dietary Potassium Supplementation for Growing Turkeys on Leg Weakness, Plasma Potassium Concentration, and Selected Blood Variables

The objectives of this research were to observe the effects of increased K in the diets of growing tom turkeys from 6 to 18 wk of age on body weight, feed-to-gain ratio, and leg weakness; to study the effects of time and temperature of blood storage after sampling and before centrifugation on plasma K concentration; and to evaluate plasma creatine kinase activity as an indicator of leg weakness. Male Nicholas White turkeys were fed corn-soybean meal based starter and grower diets from 1 d to 6 wk of age. At this time, each of three dietary treatments was assigned randomly to three pens of toms, 30 toms per pen. The dietary treatments consisted of 1) corn-soybean meal control (control) diets, 2) corn-soybean meal diets supplemented with 25% more K than the control diets contained (Mod K), and 3) corn-soybean meal diets supplemented with 50% more K than the control diets (High K). Potassium carbonate was used as the source of supplemental K for the Mod K and High K diets. Calculated K concentrations of the control diets fed from 6 to 9, 9 to 12, 12 to 15, and 15 to 18 wk were 0.84, 0.74, 0.57, and 0.54%, respectively. Results of laboratory analysis of the diets agreed closely with the calculated values.By 12 wk, toms fed the High K diets weighed less (P = 0.018) than toms fed the control diets, and this difference was still evident at 18 wk (P = 0.013), even though the High K groups were changed to the control diets at 12 wk. Toms fed the Mod K diets also tended to weigh less at 16 and 18 wk than those fed the control diets, however, the diet effect at the latter time was not significant (P > 0.05). There were no consistent effects of dietary K on feed efficiency. Total incidence of leg weakness at 12 wk was greater (P = 0.015) among toms fed Mod K and High K diets than for those toms fed the control diets. These results show that dietary K concentrations greater than those usually present in corn-soybean meal based diets for growing turkeys should be avoided.Increases in dietary K concentrations were associated with increases in plasma K concentration. Storage of blood after sampling and before centrifugation decreases the plasma concentration of K. The decrease is minimized when ambient temperature of storage is decreased. Accordingly, blood should be centrifuged immediately after sampling for accurate measurement of plasma K concentration. Plasma creatine kinase activity is not a good indicator of associated leg weakness unless physical activity and stress can be controlled before blood sampling.

MECHANISM OF ANTIHYPERTENSIVE EFFECT OF DIETARY POTASSIUM IN EXPERIMENTAL VOLUME EXPANDED HYPERTENSION IN RATS

Dietary potassium supplementation lowers blood pressure (BP) and attenuates complications in hypertensive subjects, particularly those with the low renin volume expanded (LRVE) variety. We and others have shown that the plasma level of a digitalis like substance (DLS) is elevated in this type of hypertension. We therefore, examined the effect of increases in dietary potassium on the plasma level of endogenous DLS, myocardial and renal Na+, K+-ATPase (NKA) activities, BP, and renal excretory function in reduced renal mass (RRM)-salt hypertension in the rat, a classical model of LRVE hypertension. 70% RRM rats were divided in 4 groups, namely those consuming: 1) a sodium free and normal potassium (1.3% as KCl) diet (RRM-0 Na), 2) a normal sodium and normal potassium diet (RRM-NaK), 3) a normal sodium and high potassium (2 X normal) diet (RRM-Na2K), and 4) a normal sodium and 4 times normal potassium diet (RRM-Na4K). At the end of 4 weeks of dietary treatment, direct BP was recorded, plasma level of DLS determined by bioassay and with a radioimmunoassay for digoxin (DIF) and myocardial and renal NKA activities were measured. As expected, compared to RRM-0Na rats, RRM-NaK rats developed hypertension. BP increased significantly less in RRM-Na2K, whereas BP did not increase in RRM-Na4K rats. Hypertension in RRM-NaK rats was associated with an increase in plasma DLS and DIF and decrease in renal and myocardial NKA activities. DLS was increased (DIF was not changed) and myocardial NKA also decreased in rats consuming double potassium. However, quadrupling potassium in the diet (RRM-Na4K) normalized DLS and DIF and increased myocardial and renal NKA activities, compared to RRM-0Na rats. Also compared to RRM-0Na, water consumption, urinary volume excretion, sodium, and potassium increased in the other 3 groups, more so in RRM-Na4K rats. These data show that quadrupling the potassium in the diet prevents the BP increase in RRM rats and this is associated with diuresis/natriuresis and normalization of DLS, perhaps because the diuresis/natriuresis normalizes blood volume.

Effects of dietary salt on erythrocyte and renal Na,K-ATPase activity in Dahl salt-sensitive and salt-resistant rats

This study was designed to investigate the effects of dietary salt and potassium supplementation on blood pressure and the Na,K-ATPase activity in erythrocytes and renal cortex from Dahl salt-sensitive (DS) and salt-resistant (DR) rats. Rats were fed diets containing low salt (0.4%), high salt (7%) or high salt plus potassium-citrate (K-citrate, 3%) from 5 to 10 weeks of age or from 15 to 20 weeks of age. The systolic blood pressure of DS rats measured by the tail-cuff method was significantly increased by feeding the high salt or high salt plus K-citrate diets compared with rats fed the low salt diet at both ages. The DR rats remained normotensive regardless of the dietary salt level. Supplementation of the high salt diet with K-citrate attenuated elevation of blood pressure in DS rats. The sodium content of red blood cells of DS rats fed the high salt diet was increased whereas that of DR rats fed the same diet remained unchanged. The erythrocyte Na,K-ATPase activity was not altered at 10 weeks of age by dietary salt in both strains of rats. But at 20 weeks of age, the erythrocyte enzyme activity was suppressed in DS rats fed the high salt diet and was significantly lower compared with that in DR rats fed the same diet. The renal cortex microsomal enzyme activity was decreased in both of 10-week and 20-week old DS rats fed the high salt diet. The renal cortex enzyme activity in DR rats was not changed by dietary salt levels and consequently was greater than that of DS rats when fed the high salt diet. The renal cortex Na,K-ATPase activity of DS rats was negatively correlated to blood pressure. These results suggest that the permeability of cell membrane in DS rats is increased when fed the high salt diet and consequent increases in cell sodium concentration together with suppressed Na,K-pump activity are involved in the progressive increase in blood pressure.

Dietary potassium effects on lithium concentration and toxicity in hamsters

Lithium can be toxic in rodents and human patients at concentrations within the therapeutic range for treatment of affective disorders. Diet containing supplemental potassium reduced lithium-induced weight loss in hamsters following daily injections of 3 mmol LiCl/kg for 7-10 days. Potassium supplementation also decreased lithium concentrations in peripheral tissues; but not in brain, after repeated lithium administration. Repeated lithium injection lowered the concentration of potassium in peripheral tissues, but tissue potassium was not restored by dietary potassium supplementation. Toxic effects of single injections of 1-10 mmol LiCl/kg were unaffected by dietary potassium. Lithium concentrations in plasma, brain, or peripheral tissues 6-hr after injection of 5 mmol LiCl/kg were also not altered by potassium diet. These data suggest that interactions between lithium and potassium diet differ in peripheral tissues compared to the central nervous system, and after acute versus chronic lithium administration.

Effect of potassium on vasodilation to acetylcholine in essential hypertension.

Patients with essential hypertension show impaired endothelium-dependent vasodilation induced by acetylcholine. Because dietary potassium supplementation increases endothelium-dependent relaxations to acetylcholine in hypertensive rats, we designed the present study to investigate whether potassium increases endothelium-dependent vasodilation in essential hypertensive patients. Therefore, in patients with essential hypertension (n = 13) and in normotensive control subjects (n = 13) we evaluated the effect of intrabrachial potassium chloride (0.2 mmol/min) on forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL forearm tissue per minute). In both groups of patients, potassium chloride infusion augmented local plasma potassium concentrations. Furthermore, in essential hypertensive patients but not in normotensive subjects it increased the vasodilating effect of the first three infusion rates of acetylcholine. In contrast, in seven adjunctive essential hypertensive patients, potassium chloride did not alter intrabrachial sodium nitroprusside-induced forearm vasodilation (1, 2, and 4 micrograms/100 mL forearm tissue per minute). Finally, to evaluate the role of nitric oxide on potassium-dependent facilitation of acetylcholine-induced vasodilation in essential hypertension, we studied the effect of intrabrachial NG-monomethyl L-arginine (100 micrograms/100 mL per minute) in another group of seven hypertensive patients. Vasodilation to acetylcholine was again increased by potassium chloride; NG-monomethyl L-arginine slightly blunted the vasorelaxing effect of acetylcholine but abolished the potentiating effect of potassium.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of hypothalamic-renal noradrenergic systems in hypotensive action of potassium.

To clarify the role of the renal and hypothalamic noradrenergic systems in the antihypertensive actions of dietary potassium supplementation in salt-loaded spontaneously hypertensive rats (SHR), we measured systolic blood pressure and norepinephrine turnover, which was determined from the rate of decline of tissue norepinephrine concentration after the administration of alpha-methyl-p-tyrosine, in 5-week-old SHR or age-matched Wistar-Kyoto (WKY) rats eating normal-NaCl (0.66%) or high-NaCl (8%) diet with supplementation of 8% KCl. In WKY rats, neither high-sodium nor high-potassium diets had an effect on blood pressure with no change in renal or hypothalamic norepinephrine turnover. In SHR, however, salt loading accelerated the development of hypertension. Potassium supplementation did not affect blood pressure in normal-sodium SHR but attenuated the rise in blood pressure with salt loads. Correspondingly, renal norepinephrine turnover in SHR was increased compared with that of WKY rats, and salt loading further potentiated the increased turnover in the kidney; however, no changes in hypothalamic turnover occurred. Potassium supplementation attenuated the rise in blood pressure with salt loads and the increased renal turnover. Stimulation of sympathetic discharge by cold exposure after the administration of alpha-methyl-p-tyrosine produced marked depletion of norepinephrine in most tissues. The loss of norepinephrine was significantly greater in both kidney and hypothalamus of salt-loaded SHR than in those of normal-sodium SHR, but potassium could normalize this. Thus, potassium not only diminished the increased renal norepinephrine turnover in the kidney under normal conditions but also attenuated the augmented renal and hypothalamic norepinephrine turnover by cold stress in salt-loaded SHR.(ABSTRACT TRUNCATED AT 250 WORDS)