Bradykinin stimulates renal collecting duct prorenin

Abstract

Elevated plasma prorenin (PR) is a predictor of diabetic (DM) microvascular complications. We recently identified the renal collecting duct (CD) as the major source of PR in DM and showed that angiotensin II (ANGII) receptor blockade, effectively reduces renal and plasma PR levels. We aimed to compare the effects of the ANGII receptor 1 blocker telmisartan (ARB, T), and the angiotensin converting enzyme inhibitor (ACEI), ramipril (R), on CD PR. PR content in the intact kidney was visualized in control (C) and STZ‐DM MWF rats using in vivo multi‐photon fluorescence microscopy. DM‐rats were treated for 28 days with T (ARB, 3mg/kg/day) or R (ACEI, 1mg/kg/day). Direct effects of ANGII and bradykinin (B,10nM each) on CD PR synthesis were measured using renin immunocytochemistry. STZ‐DM caused a 3‐fold increase in CD PR content which was completely abolished by T, but not by R. Also, immunoblot and renin activity measurements found that renal tissue and plasma PR levels increased 2‐fold in STZ‐DM which were prevented by T (0.8‐fold of C), but not by R (2.2‐fold). Similarly to ANGII, B increased immunoreactive PR content in cultured CD cells 35‐fold which was prevented by the B B2 receptor blocker HOE‐140. In conclusion, elevated CD PR content in DM is most effectively inhibited by ANGII receptor blockade using T and not by the blockade of the ACE using R, which effect is at least in part due to the direct stimulatory effect of B on CD PR.