Abstract:
BACKGROUND:Sodium glucose cotransporter 2 inhibitors may reduce kidney hyperfiltration, thereby preventing diabetic kidney disease progression, which may in turn reduce cardiovascular risk, including heart failure. However, the mechanisms that regulate renal function responses to sodium glucose cotransporter 2 inhibition are not yet fully understood. We explored the renal protective effects of sodium glucose cotransporter 2 inhibition with empagliflozin, with a focus on glomerular hemodynamic effects and tubuloglomerular feedback using in vivo multiphoton microscopy imaging techniques. METHODS:C57BL/6 mice and spontaneously diabetic Ins2+/Akita mice were studied. The mice were treated with empagliflozin (20 mg·kg-1·d-1) and insulin for 4 weeks, and the single-nephron glomerular filtration rate was measured using multiphoton microscope. A neuronal nitric oxide synthase inhibitor (7-nitroindazole, 20 mg·kg-1·d-1) or a cyclooxygenase-2 inhibitor (SC58236, 6 mg/L), or an A1 adenosine receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, 1 mg·kg-1·d-1) was administered to elucidate the mechanisms of tubuloglomerular feedback signaling and single-nephron glomerular filtration rate regulation. RESULTS:The urinary excretion of adenosine, nitric oxide metabolites, and the prostanoid prostaglandin E2 was also quantified. The single-nephron glomerular filtration rate in the Ins2+/Akita group was higher than in controls (C57BL/6; 4.9±1.3 nL/min versus Ins2+/Akita; 15.8±6.8 nL/min) and lower in Ins2+/Akita /empagliflozin to 8.0±3.3 nL/min (P<0.01). In vivo imaging also revealed concomitant afferent arteriolar dilation (P<0.01) and increased glomerular permeability of albumin in the Ins2+/Akita group. Empagliflozin ameliorated these changes (P<0.01). Urinary adenosine excretion in the Ins2+/Akita/empagliflozin group was higher than in Ins2+/Akita (Ins2+/Akita; 3.4±1.4 nmol/d, Ins2+/Akita/empagliflozin; 11.2±3.0 nmol/d, P<0.05), whereas nitric oxide metabolites and prostaglandin E2 did not differ. A1 adenosine receptor antagonism, but not neuronal nitric oxide synthase or cyclooxygenase-2 inhibition, blocked the effect of empagliflozin on renal function. Empagliflozin increased urinary adenosine excretion and reduced hyperfiltration via afferent arteriolar constriction, effects that were abolished by A1 adenosine receptor blockade. CONCLUSIONS:Adenosine/A1 adenosine receptor pathways play a pivotal role in the regulation of the single-nephron glomerular filtration rate via tubuloglomerular feedback mechanisms in response to sodium glucose cotransporter 2 inhibition, which may contribute to renal and cardiovascular protective effects reported in clinical trials.
journal_name
Circulationjournal_title
Circulationauthors
Kidokoro K,Cherney DZI,Bozovic A,Nagasu H,Satoh M,Kanda E,Sasaki T,Kashihara Ndoi
10.1161/CIRCULATIONAHA.118.037418subject
Has Abstractpub_date
2019-07-23 00:00:00pages
303-315issue
4eissn
0009-7322issn
1524-4539journal_volume
140pub_type
杂志文章相关文献
CIRCULATION文献大全abstract:BACKGROUND:Chemokines are important mediators of inflammatory cell recruitment that play a significant role in atherosclerosis. Fractalkine (CX3CL1) is an unusual membrane-bound chemokine that mediates chemotaxis through the CX3CR1 receptor. Recently, functional polymorphisms in the human CX3CR1 gene have been describe...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000097119.57756.EF
更新日期:2003-11-18 00:00:00
abstract:BACKGROUND:Preconditioning the heart before an ischemic insult has been shown to protect against contractile dysfunction, arrhythmias, and infarction. Pharmacological studies have suggested that fibroblast growth factor-2 (FGF2) is involved in cardioprotection. However, because of the number of FGFs expressed in the he...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000105723.91637.1C
更新日期:2003-12-23 00:00:00
abstract::To study the variability of the fraction of CPK released from the infarcted heart which enters the serum (serum entry ratio, or SER) with size and model of infarction, nine dogs underwent homogeneous infarctions (LAD ligation) of varying sizes, and 10 dogs underwent scattered infarctions (left coronary embolization). ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.58.6.1143
更新日期:1978-12-01 00:00:00
abstract:BACKGROUND:We studied the growth-promoting effects of 2 sodium pump-selective cardiotonic steroids, ouabain and marinobufagenin, on cultured cells from vascular smooth muscle (VSMCs) from human umbilical vein and a rat VSMC line, A7r5. METHODS AND RESULTS:Both ouabain and marinobufagenin activated proliferation of the...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000101919.00548.86
更新日期:2003-12-16 00:00:00
abstract::Conventional wall motion analysis of contrast ventriculograms assesses only that part of the wall that is tangential to the x-ray beam. To assess regional left ventricular function in three dimensions, a new computerized method based on densitometric analysis of digital subtraction left ventriculograms was developed a...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.77.2.457
更新日期:1988-02-01 00:00:00
abstract::The prognostic significance of a preoperative echocardiographic left ventricular end-systolic dimension (ESD) greater than 55 mm and/or fractional shortening (FS) of 25% or less was evaluated retrospectively in 84 patients who had undergone aortic valve replacement for isolated chronic aortic regurgitation due to vari...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.71.4.669
更新日期:1985-04-01 00:00:00
abstract:BACKGROUND:There are few data regarding medium-term outcome of coronary artery bypass grafting (CABG) in patients with severe left ventricular (LV) systolic dysfunction, particularly in the modern era, and even less assessing preoperative factors that might identify patients at highest risk. METHODS AND RESULTS:Three ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.000661
更新日期:2006-07-04 00:00:00
abstract:BACKGROUND:This study aimed to assess if clampless off-pump coronary artery bypass grafting (CABG) decreases risk-adjusted mortality, stroke rate, and morbidity in unselected patients in comparison to conventional CABG. METHODS AND RESULTS:Between July 2009 and November 2010, data of 1282 consecutive patients undergoi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.111.084285
更新日期:2012-09-11 00:00:00
abstract::Values for several coronary risk factors, including systolic and diastolic blood pressure, serum cholesterol, triglycerides, blood glucose, uric acid, hemoglobin, weight, vitral capacity and cigarette smoking have been found to be similar among spouses in the Framingham Study. However, longitudinal analyses show that...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.52.4.589
更新日期:1975-10-01 00:00:00
abstract:BACKGROUND:Therapy with racemic compounds produces effects that can be attributed to both (S)- and (R)-enantiomers. Here we have tested the hypothesis that an enantiomer-enantiomer interaction would modulate the effects of treatment with a racemate, the antiarrhythmic propafenone. Previous studies have shown that while...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.89.5.2396
更新日期:1994-05-01 00:00:00
abstract:BACKGROUND:The incidence, determinants, and outcome of postoperative atrial fibrillation (AF) after surgery for mitral regurgitation (MR) are poorly defined but may have important implications for timing of mitral valve surgery. METHODS AND RESULTS:In 762 patients in sinus rhythm with no AF history undergoing MR surgi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000145121.25259.54
更新日期:2004-10-19 00:00:00
abstract:BACKGROUND:Tenascin is a large extracellular matrix glycoprotein generally found in adult tissues undergoing active remodeling such as healing wounds and tumors. To determine the potential role of tenascin-C (TN-C) in the pathophysiology of atherosclerosis, we investigated the pattern of expression of TN-C in human cor...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.99.10.1284
更新日期:1999-03-16 00:00:00
abstract:BACKGROUND:Peak dP/dt is a good index of ventricular performance that is not influenced by afterload, wall motion abnormalities, or the variations in ventricular anatomy and morphology commonly encountered among patients with congenital heart disease. Unfortunately, the clinical utility of peak dP/dt has been limited b...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.88.6.2693
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:This study was designed to evaluate the effect of arglabin on the NLRP3 inflammasome inhibition and atherosclerotic lesion in ApoE2Ki mice fed a high-fat Western-type diet. METHODS AND RESULTS:Arglabin was purified, and its chemical identity was confirmed by mass spectrometry. It inhibited, in a concentrati...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.114.013730
更新日期:2015-03-24 00:00:00
abstract:BACKGROUND:Autograft reinforcement interventions (R) during the Ross procedure are intended to preserve autograft function and improve durability. The aim of this study is to evaluate this hypothesis. METHODS AND RESULTS:1335 adult patients (mean age:43.5+/-12.0 years) underwent a Ross procedure (subcoronary, SC, n=63...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.843391
更新日期:2009-09-15 00:00:00
abstract:BACKGROUND:Short-term hibernating myocardium is characterized by a decrease in contractile function in proportion to the reduced myocardial blood flow. Myocardial creatine phosphate content, initially decreased during the first minutes of ischemia, returns to near-control values, the ischemia-induced net lactate produc...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.88.2.684
更新日期:1993-08-01 00:00:00
abstract::Regional myocardial function and blood flow were determined for 48 hours after permanent occlusion of the left circumflex coronary artery in conscious swine. Systolic wall thickening and end-diastolic wall thickness (EDWTh) were correlated with regional myocardial flow (RMBF) at 15 minutes, 24 and 48 hours after occlu...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.64.4.699
更新日期:1981-10-01 00:00:00
abstract:BACKGROUND:Myocardial infarction, stroke, and sudden death undergo diurnal variation. Although genes relevant to hemostasis and vascular integrity undergo circadian oscillation, the role of the molecular clock in thrombotic events remains to be established. METHODS AND RESULTS:A diurnal variation in the time to thromb...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.107.739227
更新日期:2008-04-22 00:00:00
abstract:BACKGROUND:In subjects of all ages, those who weigh the most often have the highest blood pressure. Thus, in epidemiological studies, weight is the most important correlate of blood pressure. Using the data from the Medical College of Virginia Twin Study, we asked these questions: 1) Do the same genetic paths that regu...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.86.6.1780
更新日期:1992-12-01 00:00:00
abstract::It has been suggested that the rate of left ventricular (LV) relaxation is related to the inotropic state, end-systolic fiber length and peak LV pressure, but little information is available regarding the rate of LV relaxation in patients with coronary artery disease (CAD) and LV dysfunction. To assess the rate of LV ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.59.5.984
更新日期:1979-05-01 00:00:00
abstract:BACKGROUND:Ruling out acute myocardial infarction (AMI) on the basis of rapid assays for cardiac markers will allow early triage of patients and cost-effective use of available coronary care facilities. METHODS AND RESULTS:We studied the value of myoglobin, creatine kinase (CK)-MBmass, and troponin T in ruling out an ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.92.12.3401
更新日期:1995-12-15 00:00:00
abstract:BACKGROUND:The use of balloon coarctation angioplasty instead of surgery as treatment for unoperated coarctation of the aorta is controversial. The efficacy and complications of the two procedures have not been studied before in a prospective fashion. METHODS AND RESULTS:Thirty-six patients were prospectively randomiz...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.87.3.793
更新日期:1993-03-01 00:00:00
abstract:BACKGROUND:Hypercholesterolemia is a risk factor for coronary disease, and platelet reactivity is increased with hypercholesterolemia, suggesting a prethrombotic risk. The aim of this study was to measure mural platelet thrombus formation on an injured arterial wall in a model simulating vessel stenosis and plaque rupt...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.92.11.3172
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:Little is known about the function of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the adult heart experimentally. Moreover, whether these Ca(2+) release channels are present and play a critical role in human cardiomyocytes remains to be defined. IP3Rs may be activated after Gαq-protein-coupled receptor...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.002764
更新日期:2013-09-17 00:00:00
abstract:BACKGROUND:Left ventricular outflow tract obstruction (LVOTO) occurs in 4% to 5% of patients after prosthetic ring mitral valve repair. Major anatomic factors incriminated in the genesis of LVOTO include degenerative mitral valve insufficiency with excess leaflet tissue, nondilated left ventricular cavity, and narrow m...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::This review defines the substantial pediatric morbidity from tobacco use, including health effects on the cardiovascular system, the respiratory system, the fetus and newborn, and risk-taking behaviors of adolescents. More recent research suggests effects may extend to other areas, including reports that cigarette smo...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:10.1161/01.cir.90.5.2581
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND:Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may create an ischemic substrate conducive to sudden death, but it remains unknown whether the extent of hypertrophy is associated with proportionally poorer perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of perfusion...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.657023
更新日期:2007-05-08 00:00:00
abstract:BACKGROUND:Matricellular proteins are extracellular matrix proteins that do not contribute directly to tissue integrity but are capable of modulating cell function. We hypothesized that the matricellular protein thrombospondin (TSP)-1, a potent inhibitor of angiogenesis and activator of transforming growth factor (TGF-...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.510354
更新日期:2005-06-07 00:00:00
abstract:BACKGROUND:Human endothelial and vascular smooth muscle cells synthesize prostanoids. Several of these have been implicated in the physiological and pathophysiological regulation of vascular tone; however, there is no direct evidence that human blood vessels synthesize sufficient prostanoid to alter vessel tone. METHO...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.92.8.2113
更新日期:1995-10-15 00:00:00
abstract:BACKGROUND:Cardiac troponin I (cTnI), a sensitive and specific marker of myocardial cell injury, is useful in diagnosing and assessing prognosis in acute coronary syndromes. Small studies report that cTnI is elevated in severe heart failure (HF) and may predict adverse outcomes. METHODS AND RESULTS:The present study e...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000084543.79097.34
更新日期:2003-08-19 00:00:00