Endogenous Ouabain and Related Genes in the Translation from Hypertension to Renal Diseases

Abstract

The endogenous ouabain (EO) is a steroid hormone secreted by the adrenal gland with cardio-tonic effects. In this article, we have reviewed and summarized the most recent reports about EO, particularly with regard to how it may interact with specific genetic backgrounds. We have focused our attention on the EO’s potential pathogenic role in several diseases, including renal failure, essential hypertension and heart failure. Notably, these reports have demonstrated that EO acts as a pro-hypertrophic and growth-promoting hormone, which might lead to a cardiac remodeling affecting cardiovascular functions and structures. In addition, a possible role of EO in the development of acute kidney injury has been hypothesized. During the last decays, many important improvements permitted a deeper understanding of EO’s metabolisms and functions, including the characteristics of its receptor and the effects of its activation. Such progresses indicated that EO has significant implications in the pathogenesis of many common diseases. The patho-physiological role of EO in the development of hypertension and other cardiac and renal complications have laid the basis for the development of a new selective compound that could selectively modulate the genetic and molecular mechanisms involved in EO’s action. It is evident that the knowledge of EO has incredibly increased; however, many important areas remain to be further investigated.

DR region specific antibody ameliorated but ouabain worsened renal injury in nephrectomized rats through regulating Na,K-ATPase mediated signaling pathways

“…However, ouabain stimulated Src activation and increased renal injury. It has been proved that endogenous ouabain (or ouabain-like factors) is elevated in patients with terminal renal failure [23,24] and in renal injury –related rat models [25,26]. The binding of endogenous ouabain to the α-subunit of the Na + -K + -ATPase may directly initiate Na,K-ATPase signaling cascades and contribute to renal failure [27].…”

Ouabain Enhances Cell-Cell Adhesion Mediated by β1 Subunits of the Na+,K+-ATPase in CHO Fibroblasts

“…Therefore, it was proposed that low ouabain concentrations bind and activate a non-pumping population of the Na + ,K + -ATPase [32,33]. However, the nature of the effects that ouabain exerts at different concentrations in organisms is still controversial [34,35,36].…”

Reply: “Comment on: Endogenous Ouabain and Related Genes in the Translation from Hypertension to Renal Diseases”

“…The genomics era has allowed the development of a specific work-stream regarding EO, which is the focus of our review. Indeed, we have presented significant experimental evidence linking specific gene polymorphisms with EO, and their impact on the function of vasculature and other tissues [2].…”

“…In our recent work [2], we only described the effect of Endogenous ouabain in different pathophysiological contexts. We avoided describing the potential therapeutic effects of exogenous cardiotonic steroids because they were not the main aim of the paper.…”