Faculty Collaboration Database

Relationship between the renin-angiotensin-aldosterone system and renal Kir5.1 channels. Clin Sci (Lond) 2019 Dec 20;133(24):2449-2461

Date

12/05/2019

Pubmed ID

31799617

Pubmed Central ID

PMC8474144

DOI

10.1042/CS20190876

Scopus ID

2-s2.0-85076876405 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

Kir5.1 (encoded by the Kcnj16 gene) is an inwardly rectifying K+ (Kir) channel highly expressed in the aldosterone-sensitive distal nephron of the kidney, where it forms a functional channel with Kir4.1. Kir4.1/Kir5.1 channels are responsible for setting the transepithelial voltage in the distal nephron and collecting ducts and are thereby major determinants of fluid and electrolyte distribution. These channels contribute to renal blood pressure control and have been implicated in salt-sensitive hypertension. However, mechanisms pertaining to the impact of K ir4.1/Kir5.1-mediated K+ transport on the renin-angiotensin-aldosterone system (RAAS) remain unclear. Herein, we utilized a knockout of Kcnj16 in the Dahl salt-sensitive rat (SSKcnj16-/-) to investigate the relationship between Kir5.1 and RAAS balance and function in the sensitivity of blood pressure to the dietary Na+/K+ ratio. The knockout of Kcnj16 caused substantial elevations in plasma RAAS hormones (aldosterone and angiotensin peptides) and altered the RAAS response to changing the dietary Na+/K+ ratio. Blocking aldosterone with spironolactone caused rapid mortality in SSKcnj16-/- rats. Supplementation of the diet with high K+ was protective against mortality resulting from aldosterone-mediated mechanisms. Captopril and losartan treatment had no effect on the survival of SSKcnj16-/- rats. However, neither of these drugs prevented mortality of SSKcnj16-/- rats when switched to high Na+ diet. These studies revealed that the knockout of Kcnj16 markedly altered RAAS regulation and function, suggesting Kir5.1 as a key regulator of the RAAS, particularly when exposed to changes in dietary sodium and potassium content.

Author List

Manis AD, Palygin O, Khedr S, Levchenko V, Hodges MR, Staruschenko A

Author

Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aldosterone
Angiotensins
Animals
Blood Pressure
Gene Knockout Techniques
Kidney Tubules, Distal
Mineralocorticoid Receptor Antagonists
Potassium Channels, Inwardly Rectifying
Potassium, Dietary
Rats, Inbred Dahl
Renin-Angiotensin System
Sodium, Dietary
Spironolactone