Intrarenal generation of angiotensin II evaluated by an electrophysiological technique

Angiotensin II (ANG II) reversibly depolarizes renin-containing juxtaglomerular epithelioid cells (JGECs) of the hydronephrotic mouse kidney afferent arteriole. This depolarizing response was utilized to assess changes in ANG II concentration in the vicinity of JGECs in order to test whether ANG II is generated from ANG I and artificial renin substrate (ARS) in this preparation. Depolarizations were also produced by the application of ANG I and ARS in the superfusing medium. These responses to ANG I and ARS were completely blocked by saralasin. Hence, our findings are indicative for an intrarenal, local generation of ANG II. As opposed to saralasin, several converting enzyme and renin inhibitors only diminished but generally did not abolish the actions of ANG I and ARS, respectively. These results suggest an alternative, nonrenin and non-converting enzyme-dependent pathway of ANG II generation in renal tissue.