Renal function and blood pressure: molecular insights into the biology of endothelin-1

The therapeutic implications of the actions of endothelin (ET)-1 upon renal and cardiovascular function are evident. Among other diseases, ET-1 is recognized to be involved in hypertension and renal failure and, in a rush to develop novel treatments, has been extensively studied. However, given the broad localization of the two receptors (ET(A) and ET(B)) and the diverse effects resulting from their activation, analysis of the role of ET-1 in kidney-regulated blood pressure remains complicated. Moreover, the actions of ET-1 depend upon the cell type and physiological situation. To add to the complexity, both receptors often activate opposing signaling pathways within a single cell. Thus, until recently, reliable insights into the respective involvement of both receptors in the physiology and pathology of the kidney were eagerly awaited. These have been obtained using mice that are genetically modified for different members of the ET system. In this article, the molecular biology of ET-1 and its receptors in the control of renal vasculature tonicity, glomerular function, and management of water and salt reabsorption is discussed. The role of renal ET-1 in the context of blood pressure regulation will be discussed, and the potential of utilizing ET receptor antagonism in the treatment and prevention of glomerular and proteinuric diseases is also outlined.