Involvement of the Na+,K+-ATPase and its inhibitors in cardiovascular diseases

Abstract

⁺,K⁺-ATPase inhibitors have been shown to be effective in the treatment of congestive heart failure and cardiac arrhythmias. The Digitalis Investigation Group (DIG) trial has demonstrated that long-term digoxin treatment improves symptoms of congestive heart failure and the quality of life in patients and, unlike cyclic adenosine monophosphatase (cAMP) dependent positive inotropes, does not have a negative effect on survival. Recently, evidence has been provided that the Na⁺,K⁺-ATPase may also be functionally modulated by endogenous inhibitors, such as ouabain-like factor (OLF). Elevated OLF levels have been documented in pathological conditions, such as cardiovascular disorders and particular genetic or essential forms of human hypertension. Na⁺,K⁺-ATPase and OLF could represent a novel pharmacological target for the treatment of those forms of hypertension sustained by this mechanism. This review will cover patenting activity in this field of research and will focus on the more significant patents published over the last five years.

• antihypertensive activity
• arrhythmias
• cardenolides
• cardiac glycosides
• cardiovascular diseases
• congestive heart failure
• digitalis
• digitoxigenin
• digoxin
• endogenous digitalis-like factor
• genetic hypertension
• hypertension
• inotropic activity
• Na+,K+-ATPase
• Na+,K+-ATPase isoforms
• ouabain
• ouabain-like factor
• pregnanes
• rat models
• synthetic and endogenous Na+
• K+-ATPase inhibitors