Genetic and epidemiological studies on electrolyte transport systems in hypertension.
In recent years several different tests of cations in human cells have been studied to detect and to define possible roles in the development of essential hypertension. The goal of this report is to summarize what has been learned in genetic and epidemiological studies of human populations. The seven tests reviewed in greatest detail include sodium-lithium countertransport, intraerythrocytic sodium, sodium (or lithium)-potassium cotransport, lithium leak, sodium-potassium ATPase pump, sodium pump sites (ouabain binding), and circulating sodium pump inhibitor ('digoxin-like factor' in some studies). Countertransport, intraerythrocytic sodium and cotransport consistently show different values in hypertensives compared to normotensives and even in normotensives with a positive family history of hypertension when compared to controls without a positive family history. Thorough genetic studies have been carried out only for sodium-lithium countertransport and intraerythrocytic sodium. Both of these tests are highly heritable with a combination of both polygenic and major gene effects. Cotransport, leak, and pump sites also seem to be quite significantly heritable whereas the ATPase pump activity and the circulating pump inhibitor seem to be largely determined by nongenetic factors. Some of the most dramatic changes in these tests have been observed during pregnancy. Significant increases are seen in countertransport, cotransport, ouabain binding sites, and digoxin-like factor. Oral contraceptives also seem to affect at least cotransport. Plasma triglyceride level and body weight are some of the strongest correlates of countertransport, cotransport, and lithium leak. Cotransport increases with higher dietary sodium intake and decreases with the use of the diuretic medication. In the current developmental stage these tests have several significant limitations. In most population studies there is a considerable overlap of test values between persons with high and normal blood pressure. There are substantial variations in the methods used by different laboratories for the same tests. They are expensive, complex and usually must be done on fresh cells. There are conflicts between the results of several different reported studies that could be due to the way in which their subjects were selected, the effects of medications or other uncontrolled variables, or even due to the differences in laboratory methodologies.(ABSTRACT TRUNCATED AT 400 WORDS)
Williams
R R
RR
Department of Medicine, University of Utah School of Medicine, Salt Lake City.
Hunt
S C
SC
Wu
L L
LL
Hasstedt
S J
SJ
Hopkins
P N
PN
Ash
K O
KO
D001692:Biological Transport; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008094:Lithium / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000378:metabolism*; D011247:Pregnancy; D012964:Sodium / Q000378:metabolism*
D008094:Lithium; D012964:Sodium; D011188:Potassium