title: Angiotensin-converting enzyme inhibitor does not suppress renal angiotensin II levels in angiotensin I-infused rats.
abstract: Angiotensin II (Ang II) infusion into rats elevates local angiotensin II levels through an AT1 receptor-dependent pathway in the kidney. We examined whether treatment with an angiotensin-converting enzyme (ACE) inhibitor, temocapril, or an AT1-receptor blocker, olmesartan, prevented elevation of Ang II levels in the kidney of angiotensin I (Ang I)-infused rats. Rats were infused with Ang I (100 ng/min) and treated with temocapril (30 mg/kg per day, n = 10) or olmesartan (10 mg/kg per day, n = 9) for 4 weeks. Ang I infusion significantly elevated blood pressure compared with vehicle-infused rats (n = 6). Treatment with temocapril or olmesartan suppressed Ang I-induced hypertension. Temocapril suppressed both plasma and renal ACE activity. Ang I infusion increased Ang II content in the kidney. Interestingly, temocapril failed to reduce the level of Ang II in the kidney, while olmesartan markedly suppressed an increase in renal Ang II levels. These results suggest a limitation of temocapril and a benefit of olmesartan to inhibit the renal renin-angiotensin system and suggest the possible existence of an ACE inhibitor-insensitive pathway that increases Ang II levels in rat kidney.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Miki
authors.initials: M
authors.lastname: Murase
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pelisch
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morimoto
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.forename: Koji
authors.initials: K
authors.lastname: Ohmori
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000652:urine*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013841:Thiazepines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D013841:Thiazepines; D000804:Angiotensin II; C055603:temocapril hydrochloride; C437965:olmesartan; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A