Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems ACE and non-ACE mediated effect of angiotensin I on intracellular calcium mobilization in rat glomerular arterioles

Marchetti, Jeannine, Claudia M. B. Helou, Catherine Chollet, Rabary Rajerison, and François Alhenc-Gelas. ACE and non-ACE mediated effect of angiotensin I on intracellular calcium mobilization in rat glomerular arterioles. Am J Physiol Heart Circ Physiol 284: H1933–H1941, 2003. First published February 13, 2003; 10.1152/ajpheart.00042. 2003.—Because renin and angiotensin I (ANG I) level are high in the renal circulation, the conversion of ANG I is a critical step in the regulation of glomerular hemodynamics. We studied this conversion by investigating the effect of ANG I on intracellular Ca2 concentration ([Ca2 ]i) in rat juxtamedullary glomerular afferent and efferent arterioles (AA and EA, respectively). Two types of EA were considered, thin EA and muscular EA, terminating as peritubular capillaries and vasa rectae, respectively. In all arterioles, ANG I elicited [Ca2 ]i elevations. Maximal responses of 171 28 (AA), 183 7 (muscular EA), and 78 11 nM (thin EA) (n 6), similar to those obtained with ANG II, were observed with 100 nM ANG I. The EC50 values were 20 times higher for ANG I than for ANG II in AA (10.2 vs. 0.5) and muscular EA (6.8 vs. 0.4 nM) and 150 times higher in thin EA (15.2 vs. 0.1 nM). ANG I effect was blocked by losartan, indicating that AT1 receptors were involved. The ANG-converting enyzme (ACE) inhibitor lisinopril inhibited the maximal response to ANG I in AA and muscular EA by 75 9% (n 13) and 70 7% (n 13), respectively, but had no effect in thin EA (n 14). The serine protease inhibitor aprotinin, the chymase inhibitor chymostatin, and the cysteine protease inhibitors E64 and leupeptin had no effect on ANG I action. These data show that ANG I effects are mainly mediated by ACE in AA and muscular EA but not in thin EA. The lisinopril-insensitive response may be related to conversion by unknown enzyme(s) and/or to activation of AT1 receptors by ANG I.