The renal medullary interstitium: focus on osmotic hypertonicity.

1. There has been continued interest in the functional role of the renal medullary interstitium and intense research in this area has furnished new information regarding the extent, dynamics and mechanisms determining fluctuations in medullary osmotic hypertonicity. 2. Any change in the tonicity (interstitial solute concentration) indicates an imbalance of the rate of solute delivery to the interstitium (by tubular transport) and solute removal therefrom (by the microcirculation). It is often difficult to establish whether alteration of the delivery or removal triggered the change in medullary tissue tonicity. 3. Newer in vivo studies have confirmed earlier predictions and indirect evidence indicating that the rate of NaCl transport in the ascending limb of the loop of Henle is the major determinant of medullary ionic hypertonicity. 4. The hypothesis of a 'washout' of medullary solutes during increased medullary blood flow (MBF) has been re-evaluated. A novel experimental approach has provided direct evidence of a modest dissipation of medullary solutes with increasing MBF and a modest accumulation of solutes with decreasing MBF. 5. Increasing evidence is reviewed indicating that medullary tonicity is not only a regulated variable, but also that it may itself modulate the activity of multiple local endocrine and paracrine control systems and thereby affect local microcirculation and the function of medullary interstitial and tubular cells.