Renal vascular stress endothelial cell dysfunction, NO and renal failure


Vascular stress, endothelial cell dysfunction and reduced bioavailability of nitric oxide (NO) are important contributors of cardiovascular complications. It is known that the morbidity and mortality in cardiovascular patients are much higher in the presence of chronic renal disease, compared to patients with healthy kidneys. Kidney disease is frequently associated with changes in the expression of renal NO synthase (NOS). Our group has previously studied the function, targets and receptors of constitutive NOS. NOS activity was evaluated during NO-blockade in the Goldblatt-model and various dietary volume conditions with respect to juxtaglomerular functions of NO. The effect of reduced NO availability on the renal vascular system will be examined as a form of vascular stress. It is assumed that vascular stress results in endothelial cell dysfunction promoting vascular damage in chronic renal disease. We will focus on the role of endothelial-mesenchymal transdifferentiation and its role in aggravating fibrosis. A moderate, sub-hypertensive inhibition of NOS will be applied in normal mice and transgenic mice exhibiting fluorescent endothelia. NO-inhibitors like L-NAME (nitro-L-arginine methyl ester) and ADMA (asymmetric dimethylarginine) will be examined. The progression of the genesis from vascular damage, increase of matrix tissue and hypoxic zones in the renal parenchyma will be observed.
Head of Project:

Johannes Michael Wack
Charité - Universitätsmedizin Berlin
Institute of Vegetative Anatomy CBF
Tel. 528548
Fax 528922
johannes.wack@charite.de
Additional Head of Project:

Bachmann, Sebastian
Additional Member of Project:

Welker, Pia
Begin/End of Project:

01/2005- 12/2005
Funded by:

Universitäre Forschungsförderung Charité
Publications:

Bosse HM, Bachmann S: Immunohistochemically detected protein nitration indicates sites of renal nitric oxide release in Goldblatt hypertension. Hypertension 30: 948-952, 1997 Bachmann S, Mundel P: Nitric oxide in the kidney - Biochemistry, function and localization. Am J Kidney Diseases 24: 112-129, 1994 Oberbäumer I, Moser D, Bachmann S: Nitric oxide synthase 1 mRNA: Tissue-specific variants from rat with alternative first exons. Biol Chem 379: 913-919, 1998 Kone BC: Nitric oxide synthesis in the kidney: isoforms, biosynthesis, and functions in health. Semin Nephrol 24(4): 299-315, 2004 Ignarro LJ, Napoli C: Novel features of nitric oxide, endothelial nitric oxide synthase, and atherosclerosis. Curr Atheroscler Rep 6(4): 281-287, 2004