PhD ceremony Ms. S.L. Della Penna: Pathophysiological effects of the excess of sodium in renal and vascular tissues

PhD ceremony: Ms. S.L. Della Penna

Dissertation: Pathophysiological effects of the excess of sodium in renal and vascular tissues

Promotor(s): prof. H. van Goor, prof. B.E. Fernández

Faculty: Medical Sciences

An acute or chronic sodium overload is able to regulate the expression of AQP-1 and AQP-2 and thus the water balance through intrarenal Ang II and oxidative stress in vivo. Early renal inflammation produced by an acute excess of sodium is a process that can be prevented and/or reversed. Chronic inflammation may be reversible in the absence of histopathological lesions. Inflammation by sodium is linked to ROS (due to flux, stretch and/or transport) more tan to tubular Ang II, which could be more related to sodium and water transport. Triggering of the cascade of inflammatory events is due to an increase of the cellular work when it reabsorbs sodium, which produces relative hypoxia (HIF), increase of renal Ang II and NF-kB expression and develops oxidative stress. This cascade can be prevented or reverted by cutting the chain in any of its links: a) decreasing sodium reabsorption (ANP), b) inhibiting local Ang II (losartan) or c) the oxidative stress (tempol). In vitro, sodium can affect the expression of the Ang II receptor (AT1R) and the endothelium protecting enzyme E-NTPDase. These molecules are downregulated on the endothelium when it is co-cultured with peripheral blood mononuclear cells. A better understanding of the mechanisms involved in the regulation of water and sodium handling, especially when the body is exposed to an excess of salt, would lead to improved prevention of renal and cardiovascular diseases and would increase treatment efficacy.