Adenosine and Tubuloglomerular Feedback

During the past 16 years numerous studies have shown that adenosine is present in the normoxic kidney and accumulates when ATP hydrolysis prevails over ATP synthesis. Adenosine can induce renal vasoconstriction and a fall in glomerular filtration rate (GFR). The tubuloglomerular feed-back (TGF) mechanism refers to a series of events whereby changes in the NaCl concentration in the tubular fluid at the end of the thick ascending limb of Henle's loop are sensed by the macula densa which then elicits a twofold response in the juxtaglomerular apparatus: a change in the afferent arteriolar tone and GFR and an alteration in renin secretion from granular cells. While an increase in late proximal tubular flow rate, which increases the NaCl concentration and probably transport across the macula densa, lowers GFR and renin secretion, a low NaCl concentration at the macula densa elicits the opposite effects. One important role of the TGF response is to keep the fluid and electrolyte delivery to the distal tubule within certain limits, so that this part of the nephron can accomplish the fine adjustments in reabsorption to meet body needs. In this regard the TGF mechanism serves to establish an appropriate balance between nephron filtration rate and reabsorption in the proximal tubule and loop of Henle. Among several factors, adenosine is considered to be a potential candidate for mediating the TGF response from macula densa to extraglomerular mesangial cells, afferent arteriole, and granular cells. The TGF-mediated vasoconstriction and reduction in renin release following an elevation of the NaCl concentration at the macula densa can be blocked by theophylline and other adenosine-A1-receptor-specific antagonists. Furthermore, the TGF is potentiated by substances that can elevate extracellular adenosine concentrations such as dipyridamole. These and other findings support the concept that adenosine as a metabolic mediator may couple energy metabolism (ATP hydrolysis for tubular Na+ transport) with the control of renin secretion and GFR.