Mechanisms of gene expression in kidney of rats with stress-induced arterial hypertension (ISIAH)


We are planning to investigate mechanisms of the pathophysiology of hypertension with morphological, immunohistological and molecular biochemical techniques using a rat model. We intend to study the newly available inbred ISIAH (inherited stress induced arterial hypertension) rat of different ages and to compare these rats to normotensive WAG controls.. We specifically aim at the detection of kidney-related gene regulation in this model, which is in agreement an continuity with previous studies performed in our laboratory. The project ist focused on the morphological analysis of hypertension-related end organ damage, and on the cytochemical study of the cell specific expression and regulation of known canidate genes related with renal endocrine function (renin angiotensin system, protaglandin system, NO system) and with tubular transport (sodium chlorid cotransporters). These experiments will have to be completed by the determination of relevant plasma parameters. In addition, a differential mRNA analysis will be performed using high-throughput microarray-technique to identify differentially regulated gene products in ISIAH rats by screening rat renal libraries. Experimental protocols to influence volume balance will further be used to investigate the potential role of the identified gene products in ISIAH rat hypertension. Known genes and new gene products may be involved, and may be relevant for the phenotype and thus for the development of essential hypertension.
Head of Project:

Dr.rer.nat. Pia Welker
Charité - Universitätsmedizin Berlin
Institute of Vegetative Anatomy CBF
Tel. 450-528 777
Fax 450-528-922
pia.welker@charite.de
Additional Head of Project:

Prof. Dr. Sebastian Bachmann
Additional Member of Project:

Petra Landmann
Begin/End of Project:

01/2003- 12/2003
Funded by:

Universitäre Forschungsförderung Charité
Publications:

Bachmann S, Peters J, Engler E, Ganten D, Mullins J. Transgenic rats carrying the mouse renin gene--morphological characterization of a low-renin hypertension model. Kidney Int 1992 41(1):24-36 Bennai F, Morsing P, Paliege A, Ketteler M, Mayer B, Tapp R, Bachmann S. Normalizing the expression of nitric oxide synthase by low-dose AT1 receptor antagonism parallels improved vascular morphology in hypertensive rats. J Am Soc Nephrol 1999 10 Suppl 11:S104-15. Welker P, Schadendorf D, Artuc M, Grabbe J, Henz BM. Expression of SCF splice variants in human melanocytes and melanoma cell lines: potential prognostic implications Br J Cancer 2000 82(8):1453-8 Rapp JP. Genetic analysis of inherited hypertension in the rat. Physiol Rev 2000 80(1):135-72. Yelinova VI, Khramtsov VV, Markel AL. Manifestation of oxidative stress in the pathogenesis of arterial hypertension in ISIAH rats. Biochem Biophys Res Commun 1999 Sep 24;263(2):450-3