β2-adrenoceptor function in the kidney

Abstract

The majority of β2-adrenoceptor (β2-AR) agonists is eliminated via the kidneys as an unchanged substance. It is likely that such agents will exert pharmacological effects during their passage through the nephron. However, these pharmacological effects have, to our knowledge, not been taken into consideration when using these compounds in clinical practice because the role of β2-AR in the regulation of renal function remains unclear. Renal β2-ARs are predominantly localized to the proximal tubular epithelia and the membranes of smooth muscle cells from renal arteries. From this morphologic evidence, it is proposed that β2-AR activation may regulate glomerular function and thereby sodium and water balance in the nephron segments. Actually, β2- AR agonists given acutely cause a marked decrease in glomerular filtration rate. On the other hand, β2-AR agonists inhibit the renal production of inflammatory cytokines such as TNF-α. Furthermore, the administration of β2-AR agonists is found to attenuate apoptosis associated with shigatoxin in the hemolytic uremic syndrome (HUS). Increased understanding of the pharmacological basis of β2-AR function in the kidney provides important new information relevant to the clinical use of β2-AR agonists in airway diseases and potential applications of these drugs in renal inflammation and injury associated with sepsis or HUS.