Renal proximal tubule sodium transport and genetic mechanisms of essential hypertension

Renal sodium re-absorption is a closely regulated process serving to maintain both extracellular fluid volume and arterial blood pressure. Proteins participating in sodium re-absorption and its regulation are therefore important candidate proteins whose genes may contain sequence variation contributing to the inherited tendency for increased arterial blood pressure (essential hypertension). Important insight has come from rare forms of single-gene hypertension in human subjects and from polygenic animal models of genetic hypertension. Both indicate the primacy of altered renal function in the genesis of hypertension, and suggest that genes contributing to the disease are members of the subset of genes expressed in the kidney. This review examines evidence for abnormalities in renal sodium re-absorption in hypertension and focuses on the proximal tubule as a site of relevant dysfunction. Identification of the proteins participating in renal sodium re-absorption and its regulation, particularly those involved in the renal pressure-natriuresis mechanism, will allow gene cloning and sequencing which in turn may lead to the identification of novel gene sequence variation participating in hypertension.