The Li+-Na+ exchange and Na+-K+-Cl- cotransport systems in essential hypertension.
This review examines the physiological functions of the Li+-Na+ exchanger and Na+-K+-Cl- cotransport system in human red blood cells. Both transporters are family aggregated and determined mainly by genetic factors; they are present in kidney and vascular cells, where they are regulated by vasoactive substances. To assess the physiological function of these two transporters, we investigated their kinetic and equilibrium properties, and their modulation by vasoactive substances. Recent studies in red blood cells indicate that the Li+-Na+ exchanger may be a mode of operation of the Na+-H+ exchanger, which plays an important role in the regulation of cell pH, cell volume, and transtubular sodium transport. In vascular cells, Na+-H+ exchanger is modulated by vasoconstrictors such as growth factors and angiotensin, while Na+-K+-Cl- cotransport is modulated by vasodilators such as atrial natriuretic factor and bradykinin. Kinetic studies in red blood cells of hypertensive patients and their offspring indicate the presence of subsets with elevated Vmax of Li+-Na+ exchange or high Km for cell sodium for outward Na+-K+-Cl- cotransport. The latter alteration is found most frequently in young blacks born of hypertensive parents, and it appears to be dependent on their level of sodium intake. The relationship between the alterations of the red blood cell sodium exchanger and Na+-K+-Cl- cotransport and risk factors for hypertension indicates that they can provide a tool to examine the interaction of genetic, hormonal, and environmental factors in human hypertension.
Canessa
M
M
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Brugnara
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C
Escobales
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D017920:Antiporters; D001692:Biological Transport; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics; D002712:Chlorides / Q000097:blood*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007684:Kidney Tubules / Q000378:metabolism; D008094:Lithium / Q000097:blood*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011188:Potassium / Q000097:blood*; D012307:Risk Factors; D012964:Sodium / Q000097:blood*; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood / Q000235:genetics; D014661:Vasoconstriction
D017920:Antiporters; D002352:Carrier Proteins; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters; C045885:sodium-lithium countertransporter; D008094:Lithium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium