title: Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure.
abstract: One-hundred years ago, Starling articulated the interdependence of renal control of circulating blood volume and effective cardiac performance. During the past 25 years, the molecular mechanisms responsible for the interdependence of blood pressure (BP), extracellular fluid volume (ECFV), the renin-angiotensin system (RAS), and sympathetic nervous system (SNS) have begun to be revealed. These variables all converge on regulation of renal proximal tubule (PT) sodium transport. The PT reabsorbs two-thirds of the filtered Na(+) and volume at baseline. This fraction is decreased when BP or perfusion pressure is increased, during a high-salt diet (elevated ECFV), and during inhibition of the production of ANG II; conversely, this fraction is increased by ANG II, SNS activation, and a low-salt diet. These variables all regulate the distribution of the Na(+)/H(+) exchanger isoform 3 (NHE3) and the Na(+)-phosphate cotransporter (NaPi2), along the apical microvilli of the PT. Natriuretic stimuli provoke the dynamic redistribution of these transporters along with associated regulators, molecular motors, and cytoskeleton-associated proteins to the base of the microvilli. The lipid raft-associated NHE3 remains at the base, and the nonraft-associated NaPi2 is endocytosed, culminating in decreased Na(+) transport and increased PT flow rate. Antinatriuretic stimuli return the same transporters and regulators to the body of the microvilli associated with an increase in transport activity and decrease in PT flow rate. In summary, ECFV and BP homeostasis are, at least in part, maintained by continuous and acute redistribution of transporter complexes up and down the PT microvilli, which affect regulation of PT sodium reabsorption in response to fluctuations in ECFV, BP, SNS, and RAS.
authors.affiliation: Department of Cell and Neurobiology, University of Southern California, Los Angeles, California 90089-9142, USA. mcdonoug@usc.edu
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McDonough
mesh_terms: D000803:Angiotensin I / Q000502:physiology; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D045604:Extracellular Fluid / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D009318:Natriuresis; D012079:Renal Circulation / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D000803:Angiotensin I; D012964:Sodium