Sodium Transport: Genetics and Hypertension

BACKGROUND:

Blood pressure has a continuous unimodal distribution in the general population. Individuals with levels elevated above the 80th percentile suffer from hypertension, a major cause of cardiovascular morbidity and mortality. Over 95 percent of hypertensives have no other primary disease and are said to have essential hypertension. Pedigree and twin studies indicate that genetic differences account for a large fraction of the interindividual variation in blood pressure. In 1984 when the study began, no genetic loci had yet been identified that were useful markers for essential hypertension or served as probes into the biological basis for interindividual blood pressure variability. Environmental factors also influence blood pressure; increased dietary intake of sodium chloride, in particular, elevates blood pressure and may contribute to the development of essential hypertension in some people. It was hypothesized that genetically determined alterations in the metabolism of sodium ion occur in a subset of the population that is at increased liability to develop elevated blood pressure upon exposure to the usual range of dietary sodium intake

Reports of altered sodium transport in the red blood cells of individuals with essential hypertension and their offspring stimulated interest in this hypothesis. Several proposals were offered to explain how alterations in sodium transport similar to those observed in red blood cells could lead to elevated blood pressure when present in the renal tubules or vascular smooth muscle. Studies of the sodium-lithium countertransport system indicated that red blood cell sodium transport pathways may provide informative phenotypes that relate blood pressure and essential hypertension more closely with genetic factors.

Numerous laboratories have confirmed that the maximal rate of sodium-lithium countertransport is increased in red blood cells from individuals with essential hypertension. The sodium-lithium countertransport is normal in secondary forms of hypertension and increased levels in essential hypertension cannot be attributed to age, body size, gender or dietary salt intake. The highest levels are observed in individuals with a positive family history of essential hypertension and the lowest levels occur in normotensive controls without hypertensive relatives.

DESIGN NARRATIVE: