Expression and activity of soluble guanylate cyclase in injury and repair of anti-thy1 glomerulonephritis

Peters, Harm; Wang, Yingrui; Loof, Tanja; Martini, Sebastian; Kron, Susanne; Krämer, Stephanie; Neumayer, Hans‐H.

doi:10.1111/j.1523-1755.2004.66012.x

Cited by 27 publications

(53 citation statements)

References 34 publications

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“…In the rat mesangial proliferative model of anti-Thy-1 antibody-mediated glomerulonephritis, PAI-1, along with growth factors such as TGF-␤ and PDGF, are increased, and interventions that decrease injury also lower PAI-1 (34,35). Conversely, injecting recombinant tPA in this rat model increases plasmin generation, with subsequent decrease in matrix accumulation (36).…”

Section: Proliferative Glomerulonephritismentioning

confidence: 90%

Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease

Eddy

Fogo

2006

Journal of the American Society of Nephrology

209

189

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Section: Proliferative Glomerulonephritismentioning

confidence: 90%

Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease

Eddy

Fogo

2006

Journal of the American Society of Nephrology

209

189

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“…Cortical total RNA was extracted with TRIzol reagent (GIBCO BRL, Berlin, Germany) according to the manufacturer's instructions. The mRNA expression of TGF-␤ 1, fibronectin, PAI-1, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined by a "two-step" RT-PCR (18). A cDNA copy was created with reverse transcriptase from an RNA PCR Core kit (Roche, Applied Biosystems, Branchburg, NJ).…”

Section: Methodsmentioning

confidence: 99%

“…For analysis, a relative quantification method was used as previously described (18,19,29). Briefly, amplification is described as N ϭ N 0 ⅐ E ⌬CP , where N is the number of amplified molecules, N0 is the initial number of molecules, E is amplification efficiency, and ⌬CP is the crossing-point deviation, expressed as ⌬CP ϭ CPtarget Ϫ CPGAPDH.…”

Section: Methodsmentioning

confidence: 99%

Mycophenolate mofetil slows progression in anti-thy1-induced chronic renal fibrosis but is not additive to a high dose of enalapril

Krämer¹,

Loof²,

Martini³

et al. 2005

American Journal of Physiology-Renal Physiology

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Tubulointerstitial inflammation and fibrosis are hallmarks of chronic progressive renal diseases. To characterize the functional interaction between cell infiltration and matrix expansion, this study compared the immunosuppressant mycophenolate mofetil (MMF), intended as primarily anti-inflammatory intervention, the angiotensin-converting enzyme inhibitor enalapril, intended as primarily an anti-fibrotic drug, and a combination of both as anticipated anti-inflammatory/anti-fibrotic intervention. The model used was anti-thy1-induced chronic-progressive glomerulosclerosis (cGS) in the rat, where a brief anti-thy1-induced glomerular injury progresses spontaneously toward tubulointerstitial fibrosis and renal insufficiency. cGS was induced by injection of anti-thy1 antibody into uninephrectomized Wistar rats. One week after disease induction, animals were randomly assigned to the following groups: cGS, cGS plus MMF (20 mg·kg body wt−1·day−1), cGS plus high-dose enalapril (12 mg·kg body wt−1·day−1), and cGS plus both. At week 16 after disease induction, MMF or enalapril alone reduced signs of chronic renal disease significantly and similarly compared with the untreated cGS group. Variables measured included proteinuria, blood pressure, tubulointerstitial and glomerular matrix accumulation, expression of transforming growth factor-β1, fibronectin, and plasminogen activator inhibitor-1, infiltration of lymphocytes and macrophages, plasma creatinine and urea levels, and glomerular filtration rate. Combined MMF and enalapril treatment was not superior to single therapy. In conclusion, MMF slows the progression of chronic renal fibrosis and renal insufficiency as effectively as high-dose enalapril in the anti-thy1-induced chronic-progressive glomerulosclerosis model. The dual anti-inflammatory/anti-fibrotic intervention does not yield additive renoprotective effects, indicating that MMF and enalapril interfere with similar or very closely related pathways involved in progression of renal disease.

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“…Plasma cGMP concentrations Plasma cGMP levels were measured using an ELISA kit (BioLinx; Dynatech Laboratories, Chantilly, VA, USA) according to the manufacturer's instructions, as described previously [21]. Briefly, samples, standards and peroxidase-labelled cGMP conjugate were transferred to a microplate precoated with a cGMP-specific antibody.…”

Section: Animals and Treatmentmentioning

confidence: 99%

Enhancement of endothelial nitric oxide synthase production reverses vascular dysfunction and inflammation in the hindlimbs of a rat model of diabetes

et al. 2008

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Aims/hypothesis Reduced bioavailability of nitric oxide (NO) is a hallmark of diabetes mellitus-induced vascular complications. In the present study we investigated whether a pharmacological increase of endothelial NO synthase (eNOS) production can restore the impaired hindlimb flow in a rat model of severe diabetes. Methods A model of diabetes mellitus was induced in male Sprague-Dawley rats by a single injection of streptozotozin. Rats were treated chronically with the eNOS transcription enhancer AVE3085 (10 mg [kg body weight] −1 day −1 ; p.o.) or vehicle for 48 days and compared with controls. Endothelial function and arterial BP were investigated in vivo using an autoperfused hindlimb model and TIPcatheter measurement, respectively. Protein production of eNOS, total and phosphorylated vasodilator-stimulated phosphoprotein (VASP) were assessed in their quadriceps muscle tissue, whereas cyclic GMP (cGMP) concentrations were assessed in blood plasma. RNA levels of intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1) were measured by real-time PCR. Results Untreated diabetic rats showed significantly reduced quadriceps muscle contents of eNOS (−64%) and phosphorylated VASP (−26%) protein associated with impaired vascular function (maximum vasodilatation: −30%, p<0.05) and enhanced production of ICAM-1 (+121%) and VCAM-1 (+156%). Chronic treatment with AVE3085 did not alter arterial BP or severe hyperglycaemia, but did lead to significantly increased production of eNOS (+95%), cGMP (+128%) and VASP phosphorylation (+65%) as well as to improved vascular function (+36%) associated with reduced production of ICAM-1 (−36%) and VCAM-1 (−58%). Conclusions/interpretation In a rat model of severe diabetes, pharmacological enhancement of impaired eNOS production and NO-cGMP signalling by AVE3085 restores altered hindlimb blood flow and prevents vascular inflammation.

show abstract

Expression and activity of soluble guanylate cyclase in injury and repair of anti-thy1 glomerulonephritis

Cited by 27 publications

References 34 publications

Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease

Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease

Mycophenolate mofetil slows progression in anti-thy1-induced chronic renal fibrosis but is not additive to a high dose of enalapril

Enhancement of endothelial nitric oxide synthase production reverses vascular dysfunction and inflammation in the hindlimbs of a rat model of diabetes

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