Abstract: Disclosed herein are peptide cleavage products, generated during natural processing of epithelial sodium channel ?- and ?-subunits and their use in inhibiting epithelial sodium channel activity. Also disclosed herein are polypeptide and polypeptide analog derivatives of those agents. These epithelial sodium channel-inhibitory agents may be formulated into a drug product for, without limitation, inhibition of epithelial sodium channel function in a patient's airway, useful in treating, among other diseases or conditions: hypertension, congestive heart failure, cirrhosis, nephrotic syndrome, hypokalemia, cystic fibrosis, chronic pulmonary obstructive diseases, such as chronic bronchitis, asthma and bronchiectasis. A method of testing the activity of an epithelial sodium channel-inhibitory agent also is provided.