title: Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase.
abstract: Endothelial dysfunction in essential hypertension is an independent predictor for future cardiovascular events. Although inhibition of the renin-angiotensin system (RAS) reportedly improves endothelial function through its effects on oxidative stress and inflammation, questions remain regarding the factors that are pivotal for improvement of endothelial function by RAS inhibition. We therefore performed a prospective, randomized crossover trial in which an angiotensin II type 1 receptor antagonist, olmesartan and calcium channel blocker, amlodipine, were compared in 31 essential hypertensive patients. Results showed that, although both treatments achieved comparable lowering of blood pressure (BP), olmesartan, but not amlodipine, significantly improved endothelial function as evaluated by flow-mediated vasodilation (FMD) in the brachial artery. Although no significant changes in diabetic and lipid parameters were observed with either drug, olmesartan slightly decreased estimated glomerular filtration rate, which, surprisingly, translated into decreased microalbuminuria. In a similar vein, olmesartan reduced serum C-reactive protein and increased urine antioxidant levels compared with baseline, and reduced urine 8-epi-prostaglandin F2α levels compared with both baseline and amlodipine. Finally, although overall changes in plasma extracellular superoxide dismutase (EC-SOD) levels were not modulated by either treatment, for olmesartan there was a positive correlation between changes in FMD and those in EC-SOD levels. In conclusion, olmesartan improved endothelial function in hypertensive patients independent of its BP-lowering effect, which was due, at least in part, to its antioxidative property. Therefore, olmesartan might provide a greater long-term benefit for hypertensive patients with impaired endothelial function than amlodipine.
authors.affiliation: Division of Anti-aging, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ayaori
authors.forename: Harumi
authors.initials: H
authors.lastname: Uto-Kondo
authors.forename: Maki
authors.initials: M
authors.lastname: Iizuka
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Komatsu
authors.forename: Bonpei
authors.initials: B
authors.lastname: Takase
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ohsuzu
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikewaki
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013482:Superoxide Dismutase / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*; D014664:Vasodilation
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan; D002097:C-Reactive Protein; D013482:Superoxide Dismutase