Back to Search
Start Over
Direct regulation of ENaC by bradykinin in the distal nephron. Implications for renal sodium handling.
- Source :
-
Current opinion in nephrology and hypertension [Curr Opin Nephrol Hypertens] 2014 Mar; Vol. 23 (2), pp. 122-9. - Publication Year :
- 2014
-
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.<br />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.<br />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.
- Subjects :
- Angiotensin-Converting Enzyme Inhibitors therapeutic use
Animals
Antihypertensive Agents therapeutic use
Blood Pressure
Epithelial Sodium Channels drug effects
Genetic Variation
Humans
Hypertension drug therapy
Hypertension metabolism
Hypertension physiopathology
Nephrons drug effects
Receptor, Bradykinin B2 genetics
Receptor, Bradykinin B2 metabolism
Type C Phospholipases metabolism
Water-Electrolyte Imbalance metabolism
Water-Electrolyte Imbalance physiopathology
Bradykinin metabolism
Epithelial Sodium Channels metabolism
Nephrons metabolism
Sodium metabolism
Water-Electrolyte Balance drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1473-6543
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Current opinion in nephrology and hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 24378775
- Full Text :
- https://doi.org/10.1097/01.mnh.0000441053.81339.61