Authors: Orlov, Sergei N.; Akimova, Olga A.; Hamet, Pavel

Source: Current Hypertension Reviews, Volume 1, Number 3, November 2005 , pp. 243-257(15)

Publisher: Bentham Science Publishers

Abstract:

Vascular remodeling and hypertrophy/hyperplasia of the heart and kidney are known to be major servomechanisms of long-term maintenance of elevated blood pressure and the development of cardiovascular and renal complications seen in hypertension. Several lines of evidence suggest that these abnormalities are genetically determined and evoke an imbalance between cell proliferation and death. During the last 2 decades, it was shown that the level of cardiotonic steroids (CTS), i.e. potent and selective Na+,K+-ATPase inhibitors, is increased in several forms of volumeexpanded hypertension. We focus our review on recent data implicating CTS in the regulation of cell proliferation and death. At low concentrations, CTS augment proliferation of vascular smooth muscle cells (VSMC) as well as renal epithelial and vascular endothelial cells without significant inhibition of Na+,K+-ATPase-mediated ion fluxes. In contrast to cell proliferation, effect of CTS on cell survival is tissue-specific. In VSMC, CTS inhibit programmed cell death via a novel Na+ i-mediated, Ca2+ i-independent mechanism of expression of antiapoptotic genes including mortalin, whereas in vascular endothelial and renal epithelial cells, long-term exposure to CTS leads to cell death showing combined markers of apoptosis and necrosis. This mode of cell death is caused by interaction of CTS with Na+,K+-ATPase but is independent of inhibition of the Na+,K+-ATPase-mediated ion fluxes and inversion of the [Na+]i/[K+]i ratio. We propose that these novel signaling pathways triggered by enhanced production of endogenous CTS and/or abnormal Na+ handling contribute to cardiovascular and renal complications seen in hypertension.

Keywords: cardiotonic steroids; na+; k+-atpase; gene expression; proliferation; cell death

Document Type: Review article

DOI: http://dx.doi.org/10.2174/157340205774574559

Affiliations: 1: Laboratory of Pathophysiology of Ion Transport Disorders, Centre de recherche, CHUM -Hotel-Dieu, 3850 rue St-Urbain, Montreal, Quebec H2W 1T7, Canada.

Publication date: 2005-11-01

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• Current Hypertension Reviews publishes frontier reviews on all the latest advances on hypertension and its related areas e.g. nephrology, clinical care, and therapy. The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all clinicians and researchers in the field of hypertension.