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

Wang, Qing; Domenighetti, Andrea A.; Pedrazzini, Thierry; Burnier, Michel

doi:10.1161/01.hyp.0000178572.63064.73

Cited by 43 publications

(41 citation statements)

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“…13 Furthermore, the cardiac hypertrophy was improved by potassium supplementation in deoxycorticosterone acetate/Na mice independent of blood pressure (BP). 14 Consistent with these data, modest potassium depletion impaired LV contractile and relaxation responses to epinephrine or to preload alteration in the dog model, 15 and potassium repletion improved the LV relaxation, which was enfeebled by the restriction of potassium intake in the normal volunteers. 16 But the precise mechanism of cardiac functional improvement by potassium has not been fully elucidated.…”

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confidence: 58%

Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction

et al. 2006

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Abstract-Potassium supplementation has a potent protective effect against cardiovascular disease, but the precise mechanism of it against left ventricular abnormal relaxation, relatively early functional cardiac alteration in hypertensive subjects, has not been fully elucidated. In the present study, we investigated the effect of potassium against salt-induced cardiac dysfunction and the involved mechanism. Seven-to 8-week-old Dahl salt sensitive rats were fed normal diet (0.3% NaCl) or high-salt diet (8% NaCl) with or without high potassium (8% KCl) for 8 weeks. Left ventricular relaxation was evaluated by the deceleration time of early diastolic filling obtained from Doppler transmitral inflow, the slope of the pressure curve, and the time constant at the isovolumic relaxation phase. High-salt loading induced a significant elevation of blood pressure and impaired left ventricular relaxation, accompanied by augmentation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity in the cardiac tissue, measured by the lucigenin chemiluminescence method. Blood pressure lowering by hydralazine could not ameliorate NADPH oxidase activity and resulted in no improvement of left ventricular relaxation. Interestingly, although the blood pressure remained high, potassium supplementation as well as treatment with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, a superoxide dismutase mimetic, not only reduced the elevated NADPH oxidase activity but also improved the left ventricular relaxation. In conclusion, a high-potassium diet has a potent protective effect on left ventricular active relaxation independent of blood pressure, partly through the inhibition of cardiac NADPH oxidase activity. Sufficient potassium supplementation might be an attractive strategy for cardiac protection, especially in the salt-sensitive hypertensive subjects. Key Words: sodium Ⅲ blood pressure monitoring Ⅲ cardiac function Ⅲ heart failure Ⅲ oxidative stress Ⅲ potassium H igh-salt loading on the salt-sensitive subjects results in hypertension, left ventricular (LV) hypertrophy, and hypertensive heart failure. [1][2][3][4] The hypertensive heart failure is characterized by the LV diastolic dysfunction composed of the LV abnormal relaxation and the increased LV chamber stiffness. 5 The impaired LV active relaxation, which is observed in the patients with hypertension or diabetes, 6 has been reported recently to predict a poor prognosis, 7 thus, the preservation of the LV active relaxation from early stage may be a reasonable concept.High-salt loading on the salt-sensitive model also induces overproduction of reactive oxygen species (ROS) through activation of NADPH oxidase, 8 and ROS level had a significant positive correlation with the severity of heart failure. 9,10 In the pressure overload model by aortic banding, the impaired LV relaxation was improved effectively by antioxidant treatment, such as vitamin C or deferoxamine, indicating that excess ROS can induce LV abnormal relaxation. 11,12 To reduce ROS for cardioprotec...

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confidence: 58%

Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction

et al. 2006

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“…In analogy to previous observations (Wang et al, 2005), DOCA/salt treatment for eight weeks resulted in significant hypokalemia in uninephrectomized one renin gene mice (Table 1). At the same time, serum sodium was not changed by DOCA/salt treatment ( Table 1).…”

Section: Resultssupporting

confidence: 79%

“…We have demonstrated previously that DOCA/salt induces cardiac and renal hypertrophy, hypokalemia and metabolic alkalosis independent of blood pressure in 1-renin gene mice. Correction of hypokalemia and metabolic alkalosis by dietary potassium supplementation can prevent the development of renal and cardiac hypertrophy, as well as vascular remodeling (unpublished data) in normotensive, 1-renin gene mice that receive excess mineralocorticoid and salt (Wang et al, 2002(Wang et al, , 2005. Nevertheless, the exact mechanisms of renal and cardiovascular protection by dietary potassium in human hypertension are currently still unclear and subject of ongoing clinical trials (effects of potassium salts on blood pressure and target organ damage and potassium intake in patients with chronic kidney disease; http://clinicaltrials.gov/ct2/show/NCT00949585).…”

Section: Discussionmentioning

confidence: 97%

“…The renal and cardiovascular protector effects of a potassiumenriched diet have been described in large epidemiological studies (Ascherio et al, 1992;Khaw and Barrett-Connor, 1987;Tobian, 1988), as well as in diverse animal models (Ellis et al, 1992;Jin et al, 1999;Kido et al, 2008;Wang et al, 2005), which have demonstrated that dietary potassium supplementation prevented vascular and renal injury caused by high salt intake. In this cardiovascular protector context, a pivotal role has been assigned to the anti-hypertensive effects of potassium, as well as to other vasoprotective mechanisms, such as the reduced production of reactive oxygen species (Matsui et al, 2006) and the direct inhibition of intimal hyperplasia (Kido et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Several years ago, we have described a mouse model, which develops striking cardiac and renal hypertrophy when one renin gene mice are fed a DOCA/salt diet, notably in the absence of arterial hypertension (Wang et al, 2002), and in which cardiovascular pathology is completely prevented by dietary potassium supplementation (Wang et al, 2005). In contrast, two-renin gene mice do develop hypertension under the same condition (Wang et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Potassium restores vasorelaxation of resistance arterioles in non-hypertensive DOCA/salt fed mice

Wyss

Wang

Golshayan

et al. 2012

Microvascular Research

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Background: Potassium-enriched diets exert renal and cardiovascular protective effects, but the underlying mechanisms are largely unknown. Methods: Using the dorsal skinfold chamber model for intravital microscopy, we examined endotheliumdependent vasorelaxation of precapillary resistance arterioles in response to acetylcholine or the NO donor SNAP in awake mice. Experiments were performed in uni-nephrectomized one renin gene (Ren-1c) C57BL/6 mice (control group) and in mice having received a continuous administration of deoxycorticosterone acetate and a dietary supplementation of 1% sodium chloride for 8 weeks (DOCA/salt group). An additional group of DOCA/salt treated animals received a dietary supplement of 0.4% KCl for 3 weeks prior to the experiments (DOCA/salt + potassium group). Results: DOCA/salt treatment for 8 weeks resulted in hypokalemia, but blood pressure remained unchanged. In DOCA/salt mice, relaxation of resistance arterioles was blunted in response to acetylcholine, and to a lesser extent to SNAP, suggesting endothelial dysfunction. Endothelium-dependent vasorelaxation was restored by the potassium-enriched diet. Conclusion: This study is the first to demonstrate a protective effect of potassium on endothelium-dependent vasorelaxation in the absence of confounding anti-hypertensive effects, as observed in most animal models and the clinical situation. We propose that the known cardio-and nephro-protective effects of potassium might -at least in part -be mediated by the salutary effects on endothelium-dependent arteriolar relaxation.

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Salt and gene expression: evidence for [Na+]i/[K+]i-mediated signaling pathways

Orlov

Hamet

2014

Pflugers Arch - Eur J Physiol

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Our review focuses on the recent data showing that gene transcription and translation are under the control of signaling pathways triggered by modulation of the intracellular sodium/potassium ratio ([Na+]i/[K+]i). Side-by-side with sensing of osmolality elevation by tonicity enhancer-binding protein (TonEBP, NFAT5), [Na+]i/[K+]i-mediated excitation-transcription coupling may contribute to the transcriptomic changes evoked by high salt consumption. This novel mechanism includes the sensing of heightened Na+ concentration in the plasma, interstitial, and cerebrospinal fluids via augmented Na+ influx in the endothelium, immune system cells, and the subfornical organ, respectively. In these cells, [Na+]i/[K+]i ratio elevation, triggered by augmented Na+ influx, is further potentiated by increased production of endogenous Na+,K+-ATPase inhibitors documented in salt-sensitive hypertension.

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

Cited by 43 publications

References 44 publications

Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction

Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction

Potassium restores vasorelaxation of resistance arterioles in non-hypertensive DOCA/salt fed mice

Salt and gene expression: evidence for [Na+]i/[K+]i-mediated signaling pathways

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