Direct regulation of ENaC by bradykinin in the distal nephron. Implications for renal sodium handling

Mykola Mamenko, Oleg Zaika, Oleh Pochynyuk

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

Purpose of review 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. Recent findings 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. Summary 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.

Original languageEnglish (US)
Pages (from-to)122-129
Number of pages8
JournalCurrent opinion in nephrology and hypertension
Volume23
Issue number2
DOIs
StatePublished - Mar 2014

Keywords

  • Collecting duct
  • Connecting tubule
  • Renal kallikrein-kinin system

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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