Impact of Nitric Oxide on Renal Hemodynamics and Glomerular Function: Modulation by Atherogenic Lipoproteins?

Galle, Jan; Wanner, Christoph

doi:10.1159/000174040

Cited by 14 publications

(5 citation statements)

References 112 publications

(133 reference statements)

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“…eNOS is the only NOS expressed in glomeruli of a normal mouse kidney. In the kidney, NO has been recognized an important mediator for renal functions (10,13,19,46) and as would be expected, eNOS is expressed in human (1,18) and mouse (47) glomerular endothelial cells. iNOS has also been found expressed in mesangial cells of glomeruli, especially under various pathological conditions (32,44,45).…”

Section: Correlation Of No Measurements With Microelectrodes and Daf-2mentioning

confidence: 79%

High concentration of glucose inhibits glomerular endothelial eNOS through a PKC mechanism

Chu

Bohlen

2004

American Journal of Physiology-Renal Physiology

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Kidney glomeruli are important targets of diabetic nephropathy. We hypothesized a high concentration of glucose could suppress glomerular endothelial nitric oxide synthase (eNOS) by a protein kinase C (PKC) mechanism, as has been found in other tissues. Mouse kidney slices (150-200 microm) were bathed in Hanks' solution with 100 microM L-arginine and exposed to either 5 or 20-30 mM D-glucose. Immunofluorescence identified only eNOS in normal mouse glomeruli. Measurements of glomerular NO concentration with NO-sensitive fluorescent dye (4,5-diaminofluorescein diacetate) using confocal microscopy and NO-sensitive microelectrodes verified that resting glomeruli had active production of NO that was inhibited by N(G)-nitro-L-arginine methyl ester. High-concentration (20-30 mM) D-glucose inhibited 60-70% of the NO production within 15-30 min; L-glucose at the same concentration did not have any effect. Inhibition of PKC-beta with 100 nM ruboxistaurin prevented eNOS suppression in high-glucose media. Activation of PKC with 100 nM phorbol ester also suppressed the glomerular NO concentration. We concluded that eNOS in the renal glomerular capillary endothelial cells is suppressed by activity of PKC at high-glucose concentrations comparable to those in diabetic animals and humans. The consequence is a rapid decline in the generation of NO in the glomerular endothelial cells in the presence of a high concentration of glucose.

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Section: Correlation Of No Measurements With Microelectrodes and Daf-2mentioning

confidence: 79%

High concentration of glucose inhibits glomerular endothelial eNOS through a PKC mechanism

Chu

Bohlen

2004

American Journal of Physiology-Renal Physiology

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“…Actually, in patients with nephrotic syndrome, we found that renal plasma flow and glomerular filtration rate increased after normalizing plasma cholesterol and triglyceride levels [30], and Creager et al [31]showed that in hyperlipidemic patients the acetylcholine-induced vasorelaxation in forearm resistance vessels was attenuated. Furthermore, atherogenic lipoproteins induce formation of oxygen radicals in renal arteries, glomeruli, and juxtaglomerular cells, causing inactivation of nitric oxide and local renin release, with consequent increase in renal vascular resistance [32]. Thus, in our patients, the vasoconstrictive effect of hyperlipidemia may have potentiated the renal vasoconstriction caused by ciclosporin, enhancing and accelerating the component of renal injury caused by ciclosporin-induced renal ischemia, i.e., tubular atrophy and interstitial fibrosis.…”

Section: Discussionmentioning

confidence: 96%

Risk Factors for Chronic Renal Dysfunction in Cardiac Allograft Recipients

Esposito

Semeraro

Bellotti

et al. 2000

Nephron

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Renal dysfunction is one of the most common and threatening complications in heart transplant recipients. Even if ciclosporin seems to play a central role in inducing renal damage, other factors may concur or predispose to renal injury. In order to identify factors responsible for renal dysfunction, we retrospectively studied a cohort of 114 cardiac transplant recipients during a follow-up period of at least 3 years. The patients had a normal renal function before and 0.5 months after heart transplantation. Doubling of baseline serum creatinine or attainment of serum creatinine steadily above 176.8 µmol/l (2.0 mg/dl) was used as criterion to define the end-point renal dysfunction. A series of clinical and laboratory variables were obtained from the patients’ charts at different time intervals, and their prognostic value for the occurrence of renal dysfunction was calculated by Cox proportional hazards models. 23 out of 114 patients reached the end point after a median time period of 21 months. High serum triglyceride, alanine aminotransferase, alkaline phosphatase, ciclosporin, urea, glucose, and hemoglobin levels were shown to be associated with the development of renal dysfunction. Four variables, i.e., triglyceride, ciclosporin, urea, and alkaline phosphatase, had an independent prognostic value. Our results confirm a role for ciclosporin in inducing renal dysfunction and identify hyperlipidemia and an increased plasma urea level as risk factors for renal dysfunction in heart transplant recipients.

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“…Nitric oxide is produced in renal arteries, macula densa, glomeruli, and tubules by different nitric oxide-synthases, where it is involved in physiological regulation of renal blood flow, renal autoregulation, tubuloglomerular feedback, renin release, pressure natriuresis, and tubular function. 46 In summary, ApoE-deficient animals exhibited hypertension and endothelial dysfunction when extensive atherosclerosis had developed. Our study provides further evidence that chronic atherosclerosis in the mouse models of the disease results in pathophysiologic changes reminiscent of those found in the advanced human disease state.…”

Section: Apoementioning

confidence: 98%

Hypertension and Endothelial Dysfunction in Apolipoprotein E Knockout Mice

Yang¹,

Powell-Braxton²,

Ogaoawara³

et al. 1999

ATVB

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Abstract-Mice lacking ApoE (Apoe -/-) develop initially hypercholesterolemia and latterly atherosclerosis. This study examined hemodynamics and endothelial function in 6-week-old Apoe -/-mice with hypercholesterolemia only, 7.5-months-old Apoe -/-mice with both hypercholesterolemia and atherosclerosis, and age matched controls. One day after implantation of catheters into the carotid artery, arterial pressure was measured in conscious, unrestrained mice. Compared with the respective controls, there was a significant increase in arterial pressure and the ratio of left ventricular weight to body weight in 7.5-month-old Apoe

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Impact of Nitric Oxide on Renal Hemodynamics and Glomerular Function: Modulation by Atherogenic Lipoproteins?

Cited by 14 publications

References 112 publications

High concentration of glucose inhibits glomerular endothelial eNOS through a PKC mechanism

High concentration of glucose inhibits glomerular endothelial eNOS through a PKC mechanism

Risk Factors for Chronic Renal Dysfunction in Cardiac Allograft Recipients

Hypertension and Endothelial Dysfunction in Apolipoprotein E Knockout Mice

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