title: Angiotensin-converting enzyme-derived angiotensin II formation during angiotensin II-induced hypertension.
abstract: The extent to which endogenous angiotensin (Ang) II formation is responsible for increasing kidney Ang II content and blood pressure during Ang II-induced hypertension is unknown. To address this, mice were treated with an Ang-converting enzyme (ACE) inhibitor (ACEi) to block endogenous Ang II formation during chronic Ang II infusions. C57BL/6J male mice (8 to 12 weeks) were subjected to Ang II infusions (400 ng/kg per minute) with or without an ACEi (lisinopril, 100 mg/L in the drinking water) for 12 days. Blood pressure was monitored by tail-cuff method and telemetry. Ang II content was determined by radioimmunoanalysis. Ang II infusions increased 24-hour mean arterial pressure significantly (141.0+/-3.7 mm Hg) versus controls (110.0+/-1.0 mm Hg). ACEi prevented the increase in concentration in Ang II-infused mice (Ang II+ACEi; 114.0+/-7.4 mm Hg; P value not significant). Plasma Ang II content was significantly increased by Ang II (367+/-60 fmol/mL) versus controls (128+/-22 fmol/mL; P<0.05); plasma Ang II was not altered by ACEi alone (90+/-31) or in combination with Ang II infusions (76+/-27). Intrarenal Ang II content was significantly increased by Ang II (998+/-143 fmol/g) versus controls (524+/-60 fmol/g; P<0.05), and this was prevented by ACEi (Ang II+ACEi; 484+/-102 fmol/g; P value not significant). Thus, ACEi ameliorates the increases in blood pressure and intrarenal Ang II content caused by Ang II infusions, indicating that endogenous ACE-mediated Ang II formation plays a significant role in the increases of blood pressure and intrarenal Ang II during Ang II-induced hypertension.
authors.affiliation: Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Ave, SL39, New Orleans, LA 70112, USA. rgonzale@tulane.edu
authors.forename: Romer A
authors.initials: RA
authors.lastname: Gonzalez-Villalobos
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Satou
authors.forename: Dale M
authors.initials: DM
authors.lastname: Seth
authors.forename: Laura C
authors.initials: LC
authors.lastname: Semprun-Prieto
authors.forename: Akemi
authors.initials: A
authors.lastname: Katsurada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A