Central mineralocorticoid receptors and cardiovascular disease

Abstract

This chapter brie fl y summarizes the history of the study of mineralocorticoid receptors (MR) in the CVO of the brain, hypothalamus, amygdala, and nucleus tractus solitarius, that modulate in fl ammatory response to injury and oxidative stress in the heart and vessels, as well as homeostatic control of the hemodynamic systems, including blood pressure, water and electrolyte balance, sodium appetite, and sympathetic drive to the heart and kidney. Unfortunately, much of our current knowledge is based on pathological functions. Though the currently available MR antagonists are valuable additions to the therapy for cardiovascular and renal disease, MR are expressed in speci fi c neurons in other areas of the brain where they mediate diverse functions unrelated to the cardiovascular system, only some of which are well understood. The greatest expression of MR in the body is in the hippocampus where the receptors mediate trophic functions important to memory and cognition. Because of the crucial need to discover targets for the development of selective therapy for speci fi c MR-mediated functions, the biology of the MR, transcriptional and non-transcriptional activity, and mechanisms conferring ligand speci fi city to aldosterone is also discussed.