The macula densa
As the distal proximal tubule rises from the renal medulla, it makes close contact with the glomerulus. The cells on the side of the tubule facing the glomerulus have a distinct appearance and constitute the macular densa (Figure 1). These cells sense the NaCl content of the tubule and make changes to GFR appropriately.
A high concentration of NaCl in distal tubular fluid usually results from an excessive glomerular filtration rate (GFR), such that there is not time for the NaCl to be reabsorbed in the renal tubules. Under these circumstances, macula densa cells release adenosine, which constricts the nearby afferent arteriole, reducing glomerular perfusion and hence GFR.
On the other hand, low tubular NaCl usually results from excessive reabsorption because GFR is low. When this occurs, the macular densa cells release prostaglandin E2 (PGE2), which triggers release of renin from the granular cells (AKA juxtaglomerular cells) surrounding the afferent arteriole as it enters the glomerulus. Renin release activates the renin-angiotensin system increasing blood pressure and consequently renal perfusion.
Another way to think about GFR and NaCl reabsorption is to picture the renal tubule as a long conveyor belt shifting NaCl through the nephron. Pumps and transporters try to reabsorb sodium (like workers removing items from a conveyor belt in a factory) as it moves along. When the conveyor belt is moving slowly (low GFR) it is easy to grab every bit of NaCl off the conveyor belt before it reaches the end (the macula densa). However, if the conveyor belt is moving too quickly (high GFR), some of the NaCl is left on the belt at the end. By speeding up or slowing down the conveyor belt (GFR) you control the amount of NaCl on it at the end.
NaCl and GFR adjustments
The exact molecular details of exactly how changes in NaCl lead to adenosine or PGE2 release are still incompletely understood and the subject of ongoing research. Accumulation of Na+ in macular densa cells leads to release of adenosine (or ATP, which subsequently breaks down to adenosine), due to cell swelling as water follows excess Na+ into cells (Figure 2). The exact mechanism linking cellular swelling to adenosine/ATP release is not certain at present. Just how reduced intracellular NaCl is detected by macula densa cells and leads to PGE2 production is not well defined at present. One view holds that it is intracellular Cl- that is the trigger. PGE2 is known to be produced by cyclooxygenase-2, but just how the activity of this enzyme is regulated by Cl- (or Na+) isn't clear.