1. It is well established that pressure natriuresis plays a key role in long-term blood pressure regulation, but our understanding of the mechanisms underlying this process is incomplete.
2. Pressure natriuresis is chiefly mediated by inhibition of tubular sodium reabsorption, because both total renal blood flow and glomerular filtration rate are efficiently autoregulated. Inhibition of active sodium transport within both the proximal and distal tubules likely makes a contribution. Increased renal interstitial hydrostatic pressure (RIHP) likely inhibits sodium reabsorption by altering passive diffusion through paracellular pathways in ‘leaky’ tubular elements.
3. Nitric oxide and products of cytochrome P450-dependent arachidonic acid metabolism are key signalling mechanisms in pressure natriuresis, although their precise roles remain to be determined.
4. The key unresolved question is, how is increased renal artery pressure ‘sensed’ by the kidney? One proposal rests on the notion that blood flow in the renal medulla is poorly autoregulated, so that increased renal artery pressure leads to increased renal medullary blood flow (MBF), which, in turn, leads to increased RIHP. An alternative proposal is that the process of autoregulation of renal blood flow leads to increased shear stress in the preglomerular vasculature and, so, release of nitric oxide and perhaps products of cytochrome P450-dependent arachidonic acid metabolism, which, in turn, drive the cascade of events that inhibit sodium reabsorption.
5. Central to the arguments underlying these opposing hypotheses is the extent to which MBF is autoregulated. This remains highly controversial, largely because of the limitations of presently available methods for measurement of MBF.