WNK Kinases, Renal Ion Transport and Hypertension

Overview

Journal Am J Nephrol

Publisher Karger

Specialty Nephrology

Date 2008 Jun 13

PMID 18547946

Citations 11

Authors

Pedro San-Cristobal

Paola de Los Heros

Jose Ponce-Coria

Erika Moreno

Gerardo Gamba

Affiliations

Soon will be listed here.

Abstract

Two members of a recently discovered family of protein kinases are the cause of an inherited disease known as pseudohypoaldosteronism type II (PHAII). These patients exhibit arterial hypertension together with hyperkalemia and metabolic acidosis. This is a mirror image of Gitelman disease that is due to inactivating mutations of the SLC12A3 gene that encodes the thiazide-sensitive Na(+):Cl(-) cotransporter. The uncovered genes causing PHAII encode for serine/threonine kinases known as WNK1 and WNK4. Physiological and biochemical studies have revealed that WNK1 and WNK4 modulate the activity of several transport pathways of the aldosterone-sensitive distal nephron, thus increasing our understanding of how diverse renal ion transport proteins are coordinated to regulate normal blood pressure levels. Observations discussed in the present work place WNK1 and WNK4 as genes involved in the genesis of essential hypertension and as potential targets for the development of antihypertensive drugs.

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Disruption of the with no lysine kinase-STE20-proline alanine-rich kinase pathway reduces the hypertension induced by angiotensin II.

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Revisiting the NaCl cotransporter regulation by with-no-lysine kinases.

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