Hypertension: a disorder of volume control? what is the evidence?

Hypertension is a common trait worldwide and is responsible for a major expenditure of health-care dollars in the United States. Although the etiological factors responsible for the expression of this phenotype are complex, several experimental and clinical observations point to a major role of the kidney as responsible. Genetic studies of uncommon diseases, which express monogenetic inheritance, all have in common a dysregulation of sodium balance and volume expansion. Furthermore, epidemiological data suggest an increased incidence of hypertension in communities with high excretory rates of sodium. Experimental data also suggest that low birth weight is associated with an increase in the frequency of hypertension later in life and raises the possibility that intrauterine imprinting may contribute to the expression of the phenotype. Indeed, data suggesting up-regulation of the Na+/K+/2Cl− and thiazide-sensitive transporters in low-birth-weight animals may provide the physiological basis for these observations. Finally, subtle gain of function mutations in one or more of these transporters may unmask defects in volume homeostasis with increasing salt intake.