A Reassessment of the Pathophysiology of Progressive Cardiorenal Disorders

Heart failure and chronic renal diseases are usually progressive and only partially amenable to therapy. These disorders can be the sequelae of hypertension or worsened by hypertension. They are associated with the tissue up-regulation of multiple peptides, many of which are capable of acting within the cell interior. This article proposes that these peptides, intracrines, can form self-sustaining regulatory loops that can spread through heart or kidney, producing progressive disease. Moreover, mineralocorticoid activation seems capable of amplifying some of these peptide networks. This view suggests an expanded explanation of the pathogenesis of progressive cardiorenal disease and suggests new approaches to treatment.