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The Na-K-Cl cotransport in essential hypertension: cellular functions and genetic environment interactions
1Endocrine-Hypertension Unit, Brigham and Women's Hospital, Boston, Massachusetts.
Insights
Genetic and environmental factors influence the Na-K-Cl cotransport system, a key indicator in hypertension. This system
Area of Science:
- Physiology
- Molecular Biology
- Genetics
Background:
- The Na-K-Cl cotransport system is present in erythrocytes and vascular cells.
- Vasoactive peptides modulate this system in vascular cells.
Purpose of the Study:
- To examine factors influencing Na-K-Cl cotransport expression.
- To investigate the role of Na-K-Cl cotransport in hypertension.
Main Methods:
- Analysis of Vmax and Km for Na in human red cells.
- Observational study involving hypertensive and normotensive individuals.
- Dietary salt intake manipulation.
Main Results:
- Significant interindividual differences in Na-K-Cl cotransport Vmax, largely genetic.
- Elevated Km for Na in red cells of some Caucasian hypertensives and Black normotensives with hypertensive parents.
- Reduced Na intake normalized Km for Na in hypertensive subjects.
Conclusions:
- Na-K-Cl cotransport is a sensitive indicator of genetic and environmental influences in hypertension.
- Dietary sodium affects cotransporter kinetics in hypertensive individuals.
- Genetic predisposition and salt sensitivity are linked to Na-K-Cl cotransport function.
Abstract:
The present paper examines factors involved in the expression of the Na-K-Cl cotransport system present in erythrocytes and in vascular cells. This transport system is modulated by vasoactive peptides such as atrial natriuretic factor and bradykinin in vascular smooth muscle and endothelial cells. The Vmax of the Na-K-Cl in human red cells displays large interindividual differences which can be mainly accounted for by genetic factors. Elevation of the Km for Na of the outward Na cotransport is found in red cells of some Caucasian hypertensives and in Black normotensives born of hypertensive parents whose blood pressure increases with salt loading. Reduction of Na intake from 200 to 10 mEq/day does not influence the activity of the cotransport in normotensive individuals but decreases the Km for Na of hypertensive subjects to values similar to those of the normotensives. These findings indicate that the Na-K-Cl cotransport is an important probe of genetic and environmental factors in the hypertensive process.