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The Li+-Na+ exchange and Na+-K+-Cl- cotransport systems in essential hypertension
M Canessa1, C Brugnara, N Escobales
1Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Insights
Investigating red blood cell transporters reveals genetic links to hypertension. Altered Li+-Na+ exchanger and Na+-K+-Cl- cotransport function in families with hypertension suggests a role in disease risk.
Area of Science:
- Physiology
- Molecular Biology
- Genetics
Background:
- The Li+-Na+ exchanger and Na+-K+-Cl- cotransport system are crucial in human red blood cells.
- These transporters are genetically determined and found in kidney and vascular cells, regulated by vasoactive substances.
Purpose of the Study:
- To assess the physiological function, kinetic properties, and modulation by vasoactive substances of the Li+-Na+ exchanger and Na+-K+-Cl- cotransport system.
- To investigate the role of these transporters in hypertension.
Main Methods:
- Examined kinetic and equilibrium properties of transporters in red blood cells.
- Studied modulation by vasoactive substances.
- Analyzed transporter function in hypertensive patients and their offspring.
Main Results:
- Li+-Na+ exchanger may operate as a Na+-H+ exchanger, vital for pH, volume, and sodium transport.
- Na+-H+ exchanger is modulated by vasoconstrictors; Na+-K+-Cl- cotransport by vasodilators.
- Hypertensive patients and offspring showed altered Li+-Na+ exchange (Vmax) or Na+-K+-Cl- cotransport (Km).
- Outward Na+-K+-Cl- cotransport alteration was frequent in young Black individuals with hypertensive parents, influenced by sodium intake.
Conclusions:
- Alterations in red blood cell sodium exchanger and Na+-K+-Cl- cotransport are linked to hypertension risk.
- These transporters may serve as tools to study gene-environment interactions in hypertension.
Abstract:
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.