title: Chronic angiotensin II receptor blockade reduces (intra)renal vascular resistance in patients with type 2 diabetes.
abstract: Increased (intra)renal activity of the renin-angiotensin system may cause a persistent increase in renovascular resistance and intraglomerular pressure in patients with diabetes, thus contributing to the development of diabetic renal damage. The effect of chronic angiotensin II subtype 1 receptor blockade on (intra)renal hemodynamics in patients with type 2 diabetes was examined in a double-blind parallel group study. Patients were treated with 40 mg of olmesartan (n = 19) or placebo (n = 16), and renal hemodynamics were assessed before and after 12 wk of treatment using inulin and para-aminohippurate clearance techniques. Olmesartan significantly reduced 24-h ambulatory systolic and diastolic BP (both P < 0.05). In parallel, effective renal plasma flow increased significantly from 602 +/- 76 to 628 +/- 87 ml/min per 1.73 m(2), whereas filtration fraction and renovascular resistance decreased significantly (all P < 0.05). With placebo treatment, effective renal plasma flow decreased and filtration fraction increased significantly (both P < 0.05). GFR was not affected by both treatments. Active plasma renin concentration increased considerably (P < 0.05) with olmesartan therapy but remained unchanged with placebo treatment. Nitric oxide metabolism (plasma nitrate and nitrite) and asymmetric dimethylarginine blood levels were not affected by olmesartan and placebo therapy. In contrast, plasma 8-isoprostane 15(S)-8-iso-prostaglandin F(2a) concentration, a biochemical marker of oxidative stress, decreased significantly (P < 0.05) with olmesartan treatment. Chronic angiotensin II subtype 1 receptor blockade decreases (intra)renal vascular resistance and increases renal perfusion despite significant BP reduction. In addition, it significantly reduces oxidative stress. These effects of angiotensin II receptor antagonists may contribute to their beneficial long-term renal effects in patients with type 2 diabetes.
authors.affiliation: Department of Internal Medicine, Medical School Hannover, Germany. fliser.danilo@mh-hannover.de
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.forename: Kathrin-Kristin
authors.initials: KK
authors.lastname: Wagner
authors.forename: Astrid
authors.initials: A
authors.lastname: Loos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D000068557:Olmesartan Medoxomil; D018384:Oxidative Stress / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; C075750:8-epi-prostaglandin F2alpha; D000068557:Olmesartan Medoxomil; D015237:Dinoprost; D012083:Renin