title: Comparison of combination therapy of olmesartan plus azelnidipine or hydrochlorothiazide on renal and vascular damage in SHR/NDmcr-cp rats.
abstract: BACKGROUND
  Although the recommended target blood pressure for patients with chronic kidney disease is <130/80 mm Hg, this is difficult to achieve by treatment with an angiotensin receptor blocker alone. Addition of either a calcium channel blocker or a diuretic is suggested as second-line medication; however, which combination is most beneficial for target-organ protection remains unknown.
  
  
  METHODS
  SHR/NDmcr-cp rats were administered no medications (control) or low-dose olmesartan for 2 weeks and then either olmesartan at an increased dose, azelnidipine, or the hydrochlorothiazide for 3 weeks. We assessed oxidative stress in the kidney and aorta, and endothelial function.
  
  
  RESULTS
  Urinary protein excretion was lower in all treated rats than in control rats. Oxidative stress caused by activation of NAD(P)H oxidase was observed in the glomeruli and aorta of control rats and was significantly suppressed in the olmesartan/azelnidipine (Olm/Azl) groups. Combination therapy with olmesartan and hydrochlorothiazide (Olm/HCTZ) however failed to suppress oxidative stress. The Olm/Azl groups maintained the endothelial surface layer in the glomeruli and protected endothelial function in the aorta.
  
  
  CONCLUSIONS
  In an animal model of metabolic syndrome, a combination of Olm/Azl is superior to a combination of Olm/HCTZ in terms of prevention of glomerular and vascular injuries.
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, Japan. zajiten1@gmail.com
authors.forename: Hajime
authors.initials: H
authors.lastname: Nagasu
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yorimitsu
authors.forename: Naruya
authors.initials: N
authors.lastname: Tomita
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Kashihara
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000627:therapeutic use*; D014652:Vascular Diseases / Q000517:prevention & control*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004095:Dihydropyridines; D007093:Imidazoles; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D001383:Azetidinecarboxylic Acid; C437965:olmesartan; C061679:azelnidipine