title: Direct regulation of ENaC by bradykinin in the distal nephron. Implications for renal sodium handling.
abstract: OBJECTIVE
  Locally produced peptide hormones kinins, such as bradykinin, are thought to oppose many of the prohypertensive actions of the renin-angiotensin-aldosterone system. In the kidney, bradykinin, via stimulation of B2 receptors (B2R), favors natriuresis mostly due to the inhibition of tubular Na reabsorption. Recent experimental evidence identifies the epithelial Na channel (ENaC) as a key end effector of bradykinin actions in the distal tubular segments. The focus of this review is the physiological relevance and molecular details of the bradykinin signal to ENaC.
  
  
  RESULTS
  The recent epidemiological GenSalt study demonstrated that genetic variants of the gene encoding B2R show significant associations with the salt sensitivity of blood pressure. Bradykinin was shown to have an inhibitory effect on the distal nephron sodium transport via stimulation of B2 receptor-phospholipase C (B2R-PLC) cascade to decrease ENaC open probability. Genetic ablation of bradykinin receptors in mice led to an augmented ENaC function, particularly during elevated sodium intake, likely contributing to the salt-sensitive hypertensive phenotype. Furthermore, augmentation of bradykinin signaling in the distal nephron was demonstrated to be an important component of the natriuretic and antihypertensive effects of angiotensin converting enzyme inhibition.
  
  
  CONCLUSIONS
  Salt-sensitive inhibition of ENaC activity by bradykinin greatly advances our understanding of the molecular mechanisms that are responsible for shutting down distal tubule sodium reabsorption during volume expanded conditions to avoid salt-sensitive hypertension.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Mykola
authors.initials: M
authors.lastname: Mamenko
authors.forename: Oleg
authors.initials: O
authors.lastname: Zaika
authors.forename: Oleh
authors.initials: O
authors.lastname: Pochynyuk
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure; D001920:Bradykinin / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects; D014883:Water-Electrolyte Imbalance / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D053503:Epithelial Sodium Channels; D043782:Receptor, Bradykinin B2; D012964:Sodium; D010738:Type C Phospholipases; D001920:Bradykinin