title: ACE and non-ACE mediated effect of angiotensin I on intracellular calcium mobilization in rat glomerular arterioles.
abstract: 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 Ca(2+) concentration ([Ca(2+)](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 [Ca(2+)](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 EC(50) 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 AT(1) 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 AT(1) receptors by ANG I.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 367, Physiologie et Pathologie Expérimentale Vasculaires, Université Paris VI, France. marchett@ifm.inserm.fr
authors.forename: Jeannine
authors.initials: J
authors.lastname: Marchetti
authors.forename: Claudia M B
authors.initials: CM
authors.lastname: Helou
authors.forename: Catherine
authors.initials: C
authors.lastname: Chollet
authors.forename: Rabary
authors.initials: R
authors.lastname: Rajerison
authors.forename: François
authors.initials: F
authors.lastname: Alhenc-Gelas
mesh_terms: D000465:Algorithms; D000803:Angiotensin I / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007606:Juxtaglomerular Apparatus / Q000098:blood supply / Q000187:drug effects; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism*; D017706:Lisinopril / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D009130:Muscle, Smooth / Q000098:blood supply; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015853:Cysteine Proteinase Inhibitors; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D015842:Serine Proteinase Inhibitors; D000803:Angiotensin I; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D019808:Losartan; D002118:Calcium