A mechanism for mineralocortcoid participation in renal disease and heart failure

Various forms of chronic renal disease as well as congestive heart failure progress irrespective of currently available supportive care. Clinical evidence indicates that blockade of the renin–angiotensin system and/or mineralocorticoid inhibition are partially effective. Recently, it was suggested that the initiation of feed–forward intracrine loops such as renin–angiotensin system up–regulation can explain the progression of disease in the face of the control of initiating factors such as high glucose or hypertension. Here, these notions are expanded to include a potential interaction of mineralocorticoid activity with intracrine renin–angiotensin system up–regulation. In addition to suggesting therapeutic interventions, these observations lead to an expanded view of intracrine physiology.