Kidney, salt, and hypertension: how and why

A hypothesis is proposed that the aberrant response of the tubuloglomerular feedback to salt load is the abnormality in the kidney in the genesis of essential hypertension. This thesis is based upon the following facts on the kidney, salt and hypertension. To effectively achieve the primary function of the kidney, that is, to maintain the milieu interieur or the extracellular fluids, the kidney must maintain a high glomerular filtration rate (GFR) and almost a complete tubular reabsorption in the face of limited salt intake or low ECF volume and in the face of changes in systemic blood pressure. Autoregulation of renal blood flow and GFR is therefore critical. In addition to myogenic responses in the resistant afferent artery, the juxtaglomerular apparatus (JGA) plays a crucial role in the autoregulation of renal plasma flow and GFR through tubuloglomerular feedback (TGF). That the JGA and TGF have appeared first in amphibian species in evolution suggests that the transition from aquatic sea life, where salt is always in excess to terrestrial life, required this particular structure and function of the kidney. Salt intake in the natural environments on land is very limited, and chronic excess salt intake is a habit peculiar to humans in recent culture or civilization. Thus, it is hypothesized that through evolution the TGF is primarily set to maintain high GFR in the face of low salt intake. We propose that aberrant TGF responses to salt loading may underlie the genesis of essential hypertension in humans. Indeed, hypertension is not seen in human cultures that ingest a very low salt intake.