Chronic potassium depletion induces renal injury, salt sensitivity, and hypertension in young rats

Ray, Patricio E.; Suga, Shin-ichi; Li, Xuehui; Huang, Xian; Johnson, Richard J.

doi:10.1046/j.1523-1755.2001.0590051850.x

Cited by 91 publications

(57 citation statements)

References 33 publications

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“…32 Eventually, peritubular capillaries are permanently damaged and reduced in number, thus causing ischemia, increasing the oxidative stress, and mediating tubulointerstitial inflammation and impairment of pressure diuresis. In support of this hypothesis, a reduction in peritubular capillary density was demonstrated in experimental models of SSHTN [33][34][35] and in humans with essential hypertension. 36 Hypertension and tubulointerstitial inflammation Although not emphasized in the 1958 classical study of Sommers et al, 27 inflammatory infiltration was a constant feature in the renal biopsies of hypertensive patients and, more importantly, the authors did note 'collections of lymphocytes' in the renal interstitium in about 20% of the hypertensive patients that had minimal or no arteriolar changes.…”

Section: Renal Microvascular Disease and Interstitial Inflammation Armentioning

confidence: 63%

The role of renal microvascular disease and interstitial inflammation in salt-sensitive hypertension

Rodríguez‐Iturbe¹,

Johnson

2010

Hypertens Res

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Primary (essential) hypertension has been shown to be mediated by a relative impairment in sodium excretion by the kidney, but the mechanisms responsible for this defect are still being clarified. Increasing evidence suggests a role for subtle acquired renal injury in mediating this process. Microvascular injury is present in the majority of subjects with hypertension. The development of arteriolosclerosis, primarily of the afferent arteriole, may interfere with glomerular autoregulation, whereas the loss of peritubular capillaries may facilitate local ischemia. These changes favor the localization of T cells and macrophages into the interstitium, which, coupled with local oxidative stress and angiotensin II generation, may contribute to the impaired pressure natriuresis observed with salt-sensitive hypertension. Consistent with this hypothesis, therapies that are aimed at blocking the immune response, including thymectomy, genetic alterations in mice resulting in impaired immune responses, or the use of immunosuppressive agents, can protect against the development of hypertension in experimental models. Preliminary data in humans also suggest that the inhibition of the renal inflammatory response may reduce blood pressure. The present investigations are directed to gain insight in the role of the intrarenal T-cell reactivity and autoimmunity in driving the tubulointerstitial inflammation and its participation in the pathogenesis of salt-sensitive hypertension.

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Section: Renal Microvascular Disease and Interstitial Inflammation Armentioning

confidence: 63%

The role of renal microvascular disease and interstitial inflammation in salt-sensitive hypertension

Rodríguez‐Iturbe¹,

Johnson

2010

Hypertens Res

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“…Dietary potassium restriction stimulates the release of renal renin and AngII (13,14). AngII exerts its physiological effects by binding to AT1 and AT2 receptors.…”

mentioning

confidence: 99%

Angiotensin II Inhibits the ROMK-like Small Conductance K Channel in Renal Cortical Collecting Duct during Dietary Potassium Restriction

Wei

Zavilowitz

Satlin

et al. 2007

Journal of Biological Chemistry

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Base-line urinary potassium secretion in the distal nephron is mediated by small conductance rat outer medullary K (ROMK)-like channels. We used the patch clamp technique applied to split-open cortical collecting ducts (CCDs) isolated from rats fed a normal potassium (NK) or low potassium (LK) diet to test the hypothesis that AngII directly inhibits ROMK channel activity. We found that AngII inhibited ROMK channel activity in LK but not NK rats in a dose-dependent manner. The AngII-induced reduction in channel activity was mediated by AT1 receptor (AT1R) binding, because pretreatment of CCDs with losartan but not PD123319 AT1 and AT2 receptor antagonists, respectively, blocked the response. Pretreatment of CCDs with U73122 and calphostin C, inhibitors of phospholipase C (PLC) and protein kinase C (PKC), respectively, abolished the AngIIinduced decrease in ROMK channel activity, confirming a role of the PLC-PKC pathway in this response. Studies by others suggest that AngII stimulates an Src family protein-tyrosine kinase (PTK) via PKC-NADPH oxidase. PTK has been shown to regulate the ROMK channel. Inhibition of NADPH oxidase with diphenyliodonium abolished the inhibitory effect of AngII or the PKC activator phorbol 12-myristate 13-acetate on ROMK channels. Suppression of PTK by herbimycin A significantly attenuated the inhibitory effect of AngII on ROMK channel activity. We conclude that AngII inhibits ROMK channel activity through PKC-, NADPH oxidase-, and PTK-dependent pathways under conditions of dietary potassium restriction.

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“…Pere et al (29,30) reported that a high-potassium diet (2.4% potassium) is renoprotective in cyclosporine-induced nephrotoxicity, compared with a diet containing 0.8% potassium. In contrast, chronic potassium depletion causes renal functional deterioration, interstitial nephritis, or cyst formation in animals and humans (3,4,6,11,32,34,40,47). The proposed underlying mechanisms of the deleterious effect of potassium depletion include activation of the local renin-angiotensin II system (RAS) (32), increased angiotensin II receptor (AT 1 ) expression (12), and altered activity of the sodium-potassium pump in the renal tubule (35), acting by blood pressure-dependent and/or blood pressureindependent mechanisms.…”

mentioning

confidence: 99%

Renal inflammation is modulated by potassium in chronic kidney disease: possible role of Smad7

Wang¹,

Soltero²,

Zhang³

et al. 2007

American Journal of Physiology-Renal Physiology

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High-potassium diets have been shown to be beneficial in cardiovascular disease partly because of a blood pressure-lowering effect. The effect of potassium on inflammation has not been studied. We investigated the influence of potassium supplementation on the degree of renal inflammation and the intracellular signaling mechanisms that could mediate inflammation in chronic kidney disease (CKD). CKD was created in male SpragueDawley rats by subtotal nephrectomy. Two groups of CKD rats were pair fed with diets containing 2.1% potassium (potassium-supplemented diet) or 0.4% potassium (basal diet). Body weight, blood pressure, and blood and urine electrolytes were measured biweekly. The animals were euthanized at week 8, and the remnant kidneys were analyzed by histology, immunohistochemistry, Western blotting, and real-time quantitative PCR. In the CKD pair-fed groups, blood potassium concentration did not differ significantly, but blood pressure was lower in the potassium-supplemented group. Compared with the basal diet, potassium supplementation decreased renal tubulointerstitial injury and suppressed renal inflammation as evidenced by decreased macrophage infiltration, lower expression of inflammatory cytokines, and decreased NF-B activation. These renoprotective effects were associated with downregulation of renal transforming growth facto-␤, upregulation of renal Smad7, and lower blood pressure. Our results show that potassium supplementation can reduce renal inflammation and hence, could modulate the progression of kidney injury in CKD.NF-B; potassium; Smad7; TGF-␤ THE MEDIATORS OF PROGRESSIVE chronic kidney disease (CKD) remain largely unsolved, especially the mechanisms leading to progressive fibrosis of the kidney. The presence of fibrosis in the kidney is generally preceded by glomerular and tubulointerstitial infiltration by inflammatory cells. It is likely that the infiltrating inflammatory cells activate NF-B, leading to the production and release of proinflammatory cytokines and adhesion molecules (e.g., IL-1␤, ICAM-1) as well as profibrotic cytokines [e.g., transforming growth factor (TGF)-␤]. The consequence is renal inflammation and progressive fibrosis of the kidney, leading to loss of function. Treatment strategies have included medications and dietary modifications such as limitation of protein and sodium intake to reduce the accumulation of potential uremic toxins and blood pressure. The potential influence of potassium intake on progressive kidney disease remains largely unknown.There are indications that potassium supplementation may be beneficial in cardiovascular diseases, especially for problems arising as a complication of hypertension (7,17,20,27,38). There are also indications that potassium supplementation might reduce local vascular inflammatory reactions. Ishimitsu et al. (16) reported that potassium supplementation suppressed macrophage activity in stroke-prone spontaneously hypertensive rats (SHPsp). In their study, the rats were fed a normal or high-potassium diet, and excised aort...

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Chronic potassium depletion induces renal injury, salt sensitivity, and hypertension in young rats

Abstract: Dietary potassium deficiency per se increases the BP in young rats and induces salt sensitivity that may involve at least two different pathogenic pathways: increased RAS activity and induction of tubulointerstitial injury.

Cited by 91 publications

References 33 publications

The role of renal microvascular disease and interstitial inflammation in salt-sensitive hypertension

The role of renal microvascular disease and interstitial inflammation in salt-sensitive hypertension

Angiotensin II Inhibits the ROMK-like Small Conductance K Channel in Renal Cortical Collecting Duct during Dietary Potassium Restriction

Renal inflammation is modulated by potassium in chronic kidney disease: possible role of Smad7

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