Abstract:
BACKGROUND:Endothelium-derived nitric oxide and reactive oxygen species (ROS) have been proposed to regulate vascular tone by complex mechanisms, including the modulation of ion channel function. In endothelial function itself, activation of Ca2+-activated K+ channels (KCa) plays a crucial role by inducing hyperpolarization, which promotes membrane potential-driven Ca2+ influx and Ca2+-dependent synthesis of vasodilatory factors. In the present study, we tested whether nitric oxide and ROS modulate endothelial KCa function. METHODS:By employing the patch-clamp technique in endothelium of porcine renal arteries in situ, we identified a large-conductance Ca2+-activated K+ channel (big K+ channel, BKCa) with a conductance of 297 +/- 6 pS. RESULTS:Channel activity was strongly controlled by the membrane potential and the cytosolic Ca2+ concentration (EC50 3.1 +/- 0.5 micromol/L Ca2+ at 0 mV). Channel activity was inhibited by Ba2+ and iberiotoxin. At submicromolar [Ca2+]i, nitric oxide induced a dose-dependent stimulation of BKCa activity with a 10-fold increase at the highest dose tested (1 micromol/L). A similar stimulation was achieved by the nitric oxide donors, sodium nitroprusside (SNP), and diethylamine nitric oxide complex (DEA-NO). In contrast, ROS and, in particular, hydrogen peroxide (H2O2) led to dose-dependent inactivation of BKCa with an IC50 of 80 +/- 6 nmol/L and 1.1 +/- 0.4 micromol/L, respectively. In isolated porcine renal arteries, bradykinin-induced vasodilation was significantly reduced by either iberiotoxin or H2O2. CONCLUSION:Direct stimulation of endothelial BKCa by nitric oxide might represent a novel mechanism of autocrine regulation of endothelial function and points to a positive feedback mechanism by promoting hyperpolarization and nitric oxide production itself. The ROS-induced inhibition of BKCa could be part of the cellular mechanisms by which ROS impairs endothelium-dependent vasodilation.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Brakemeier S,Eichler I,Knorr A,Fassheber T,Köhler R,Hoyer Jdoi
10.1046/j.1523-1755.2003.00051.xsubject
Has Abstractpub_date
2003-07-01 00:00:00pages
199-207issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49307-Xjournal_volume
64pub_type
杂志文章abstract:BACKGROUND:Microarray technology is a powerful tool that can probe the molecular pathogenesis of renal injury. In this present study microarray analysis was used to monitor serial changes in the renal transcriptome of a rat model of mesangial proliferative glomerulonephritis. Administration of anti-Thy1 antibody result...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00661.x
更新日期:2005-12-01 00:00:00
abstract::The early identification of renal transplant recipients at enhanced risk of developing acute and subclinical rejection would allow individualized adjustment of immunosuppression before functional graft injury occurs and would exclude these patients from drug-weaning studies. Protein and reverse transcriptase-polymeras...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000343
更新日期:2006-05-01 00:00:00
abstract::Previous studies from our laboratory have demonstrated that metabolic clearance rate (MCR) of calcitriol is decreased in experimental renal failure. In this experiment, we examined the effects of calcitriol, 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) on the MCR of calcitriol in renal ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.185
更新日期:1989-08-01 00:00:00
abstract::Zhang et al. found that plasma concentrations of the thiamine antimetabolite oxythiamine are significantly increased in patients with end-stage renal disease. These investigators discuss the potential sources of oxythiamine and the consequences of its plasma elevation. This commentary addresses the significance of the...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.04.017
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Lipid peroxidation impairs renal function. Aldosterone contributes to renal injury in the remnant kidney model. This study aimed to determine the effects of the antioxidant N-acetylcysteine (NAC) on renal function and aldosterone levels in chronic renal failure. METHODS:Adult male Wistar rats were submitted...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00677.x
更新日期:2005-11-01 00:00:00
abstract::In hemodialysis patients with hyperkalemia, i.v. sodium bicarbonate has recently been found to be ineffective in lowering plasma potassium within one hour. In the present study the effect of a prolonged bicarbonate infusion on plasma potassium was investigated. Twelve patients with terminal renal failure who were on h...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.51
更新日期:1992-02-01 00:00:00
abstract:BACKGROUND:Previous reports have shown the presence of erythrogenic toxin type B (ETB), apoptosis, proliferation, and leukocyte infiltration in biopsies from patients with acute poststreptococcal glomerulonephritis (APSGN). METHODS:Attempting to correlate the apoptotic and proliferative events with the interaction of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059003950.x
更新日期:2001-03-01 00:00:00
abstract::The adjuvanted hepatitis B vaccine, HB-AS04, elicits more rapid and persistent protective antibody concentrations than double doses of conventional recombinant vaccines in patients with renal insufficiency. We compared the immunogenicity, reactogenicity, and safety of the AS02(V)-adjuvanted hepatitis B vaccine HB-AS02...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2009.454
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Transplantation is the optimal therapy for pediatric end-stage renal disease (ESRD) patients, but in a subset of patients with peritoneal membrane failure, failed transplants or poor social situations, chronic hemodialysis (HD) remains the only option. Long-term survival of arteriovenous fistulas (AVFs) and ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00630.x
更新日期:2002-11-01 00:00:00
abstract::The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.40
更新日期:1997-01-01 00:00:00
abstract::Atrial natriuretic peptide (ANP) is known to suppress platelet-derived growth factor (PDGF)-stimulated proliferation of rat cultured vascular smooth muscle cells. The present study examined whether ANP inhibits the PDGF receptor (PDGFR) tyrosine kinase activation, an initial event for PDGF cellular signaling. ANP redu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.341
更新日期:1997-08-01 00:00:00
abstract:BACKGROUND:The fluid filling renal cysts in human polycystic kidneys is secreted chiefly by the tubular epithelium lining the cysts via secondary chloride transport. Inhibiting this process by somatostatin therapy should induce shrinking of renal cysts. METHODS:In this randomized, cross-over, placebo-controlled trial ...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00395.x
更新日期:2005-07-01 00:00:00
abstract::The present study examined the effect of elevated glucose on glomerular cell membrane lipid peroxidation. Glomeruli were isolated from male Sprague-Dawley rat kidneys utilizing a standard sieving method and incubated in medium containing different concentrations of glucose at 37 degrees C for one and 48 hours. The lev...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.461
更新日期:1994-12-01 00:00:00
abstract::Absorption of amino acids by the necturus proximal tubules was measured under free-flow conditions The coexistence of proximal tubular amino acid influx was determined by infusing saline into tubular lumens by the stopped-flow microperfusion technique. Under free-flow conditions, fractional absorption of individual am...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1978.67
更新日期:1978-06-01 00:00:00
abstract::The recent identification of RPGRIP1L as a Joubert syndrome gene brings the total of known genes to five. Three of these are also associated with the lethal Meckel syndrome, and two with Senior-Løken syndrome; both of these disorders share Joubert syndrome phenotypes, illustrating the genetic complexity of this. ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002577
更新日期:2007-12-01 00:00:00
abstract::Donor pretreatment of 100 mg/kg each of cyclophosphamide (CY) and methylprednisolone (P) infused 5 hours before nephrectomy invariably prolongs the survival of DLA mismatched, MLC incompatible nonlittermate Beagle renal allografts as well as the survival of mongrel renal allografts. The effect of donor pretreatment ap...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.25
更新日期:1982-02-01 00:00:00
abstract::The presence of CR1 mRNA in podocytes was investigated using a 35S-labeled CR1 cDNA probe and in situ hybridization in sections from fetal and adult human kidneys. CR1 mRNA was only detected in immature podocytes at early stages of glomerular differentiation in the fetal kidney. In contrast, CR1 antigen was abundantly...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.198
更新日期:1990-08-01 00:00:00
abstract::The autoregulatory ability of the renal vascular system in the split hydronephrotic kidney was quantitated with intravital microscopy. The luminal diameters of the arcuate and interlobular arteries as well as the afferent and efferent arterioles were measured. Glomerular blood flow was determined by the dual slit tech...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.104
更新日期:1989-05-01 00:00:00
abstract:BACKGROUND:We aimed to identify genes with kidney specific, developmentally regulated expression. Here we report the cDNA sequence and expression pattern of KS, a novel kidney-specific rat gene. METHODS:A partial cDNA was identified by differential display polymerase chain reaction (PCR) of a renal cell fraction enric...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00143.x
更新日期:1998-11-01 00:00:00
abstract::Coronary artery stenosis induces renal inflammation and kidney injury in pigs even in the absence of myocardial infarction or clinically significant heart failure. This effect is aggravated by experimentally induced renovascular hypertension. Interestingly, oxidative stress originating from the ischemic myocardium was...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.431
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND:Pre-eclampsia is characterized by hypertension, proteinuria and edema. Simultaneous studies of kidney function and structure have not been reported. We wished to explore the degree and nature of glomerular dysfunction in pre-eclampsia. METHODS:Physiologic techniques were used to estimate glomerular filtrati...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00097.x
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND:Dopamine (DA) is thought to regulate renal proximal transport through the inhibition of the Na+,K+-ATPase and/or Na+/H+ exchanger. Defects in this dopaminergic system are proposed to be a pathogenic factor of genetic hypertension. However, microperfusion studies have not consistently confirmed direct tubular...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00873.x
更新日期:2000-02-01 00:00:00
abstract::Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney diseas...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.12.008
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Patients on continuous ambulatory peritoneal dialysis (CAPD) are dependent on residual renal function for solute and water clearances, and this declines with time on dialysis. Loop diuretics have been postulated to slow this decline. METHODS:Sixty-one patients new to dialysis were randomly assigned to eithe...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.0590031128.x
更新日期:2001-03-01 00:00:00
abstract::Mitochondrial diseases represent a significant clinical challenge. Substantial efforts have been devoted to identifying therapeutic strategies for mitochondrial disorders, but effective interventions have remained elusive. Recently, we reported attenuation of disease in a mouse model of the human mitochondrial disease...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.08.038
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Nuclear factor-kappaB (NF-kappaB) and activated protein-1 (AP-1) are transcription factors that regulate many genes involved in the progression of renal disease. Recent data have shown that NF-kappaB is activated in tubules and glomeruli in various experimental models of renal injury. In vitro studies also s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00941.x
更新日期:2001-10-01 00:00:00
abstract:BACKGROUND:Microalbuminuria (MA) is a strong predictor of cardiovascular disease, but its causes are incompletely understood. Hyperhomocysteinemia is a recently recognized risk factor for cardiovascular disease independent of established risk factors. It is not known whether hyperhomocysteinemia is associated with MA, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.4495353
更新日期:1998-07-01 00:00:00
abstract::The purpose of these studies was to clarify the basis of the relationship between the urine bicarbonate concentration and the urine minus blood PCO2 difference in alkaline urine (U-B PCO2) and hence shed light on factors that influence hydrogen ion secretion in the collecting duct in vivo. The U-B PCO2 was used to mon...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.187
更新日期:1981-11-01 00:00:00
abstract::Serum calcitriol and the free calcitriol index together with factors considered to regulate calcitriol production were measured in eleven patients with moderate chronic renal failure (MCRF) and eleven age- and sex-matched normal subjects. Although the serum dialysable calcium levels were similar in the two groups, the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.58
更新日期:1988-03-01 00:00:00
abstract::Reducing proteinuria and blood pressure in chronic kidney disease (CKD) decreases rate of progression. Inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers is beneficial in reducing proteinuria but incomplete in suppressing aldosterone production a...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/sj.ki.5002007
更新日期:2006-12-01 00:00:00