Chronic Regulation of Na/H Exchanger NHE3 by Dopamine

University Of Texas Sw Med Ctr/Dallas, Dallas TX

Investigators

Abstract

DESCRIPTION (provided by applicant): The intrarenal autocrine/paracrine dopamine system is a pivotal natriuretic efferent arm for sodium homeostasis and blood pressure regulation. Dopamine effects natriuresis by direct inhibition of Na transporters such as the Na/H exchanger-3 (NHE3). While acute natriuretic responses are important for sudden changes in effective arterial volume, the chronic effectors are critical in terms of adaptation to changes in dietary salt intake and are more relevant to human salt-sensitive hypertension. The chronic effect of dopamine on NHE3 is relatively unexplored to date. The long-term goal is to decipher how the kidney regulates sodium excretion and determines blood pressure. The immediate objective is to work out the mechanisms by which dopamine chronically regulates NHE3. Specifically, the effect of dopamine on NHE3 protein translation and degradation will be examined in a cell culture model.