Endothelin-1 stimulates the Na+/H+ and Na+/HCO3- transporters in rabbit renal cortex.
Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor identified to date, raising the strong possibility of its involvement in the pathogenesis of systemic hypertension. Whether ET-1 exerts a direct stimulating effect on sodium reabsorption in the renal proximal convoluted tubule, the dominant locus of sodium reabsorption in the nephron, is currently unknown. Such an effect would suggest yet another mechanism by which ET-1 might mediate systemic hypertension. In studies on membrane vesicles prepared from rabbit renal cortex, we show that ET-1 (10(-8) to 10(-11) M) exerts dose-dependent stimulation of the apical Na+/H+ exchanger and the basolateral Na+/HCO3- cotransporter; preincubation of vesicles with 10(-10) M ET-1 for five minutes enhanced the activity of each transporter by approximately 25%. This stimulation reflected an increase in the Vmax of each transporter but no change in the Km for sodium. The stimulatory effect of ET-1 was blocked in the presence of an ET-1 antiserum. Moreover, the stimulation of the apical Na+/H+ exchanger and the basolateral Na+/HCO3- cotransporter by ET-1 displayed specificity as indicated by the lack of effects on the activities of the apical Na(+)-glucose transporter and the basolateral Na(+)-succinate transporter. The data implicate ET-1 as a novel, direct and specific modulator of sodium reabsorption in the proximal tubule. As such, ET-1 might be a direct determinant of extracellular fluid volume under normal and pathophysiologic circumstances, including hypertensive disorders.
Eiam-Ong
S
S
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts.
Hilden
S A
SA
King
A J
AJ
Johns
C A
CA
Madias
N E
NE
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers
D001639:Bicarbonates; D002352:Carrier Proteins; D016232:Endothelins; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium