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Arterioscler Thromb Vasc Biol

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1 Arterioscler Thromb Vasc Biol
Pravastatin Enhances Beneficial Effects of Olmesartan on Vascular Injury of Salt-Sensitive Hypertensive Rats, via Pleiotropic Effects by Eiichiro Yamamoto, Takuro Yamashita, Tomoko Tanaka, Keiichiro Kataoka, Yoshiko Tokutomi, Zhong-Fang Lai, Yi-Fei Dong, Shinji Matsuba, Hisao Ogawa, and Shokei Kim-Mitsuyama Arterioscler Thromb Vasc Biol Volume 27(3): March 1, 2007 Copyright © American Heart Association, Inc. All rights reserved.

2 Figure 1. Time course of vascular NADPH oxidase (A), superoxide (B), eNOS activity (C), and plasma NO2/NO3 (D) in DS rats. Figure 1. Time course of vascular NADPH oxidase (A), superoxide (B), eNOS activity (C), and plasma NO2/NO3 (D) in DS rats. High Na, 8% NaCl diet; Low Na, 0.3% NaCl diet. Values are mean±SEM (n=5). Eiichiro Yamamoto et al. Arterioscler Thromb Vasc Biol. 2007;27: Copyright © American Heart Association, Inc. All rights reserved.

3 Figure 2. Effect of vehicle (V), olmesartan (O), pravastatin (P), combined olmesartan and pravastatin (O+P), and hydralazine (H) on acetylcholine-induced vascular relaxation (A), coronary arterial thickening (B), and perivascular fibrosis (C) of DS rats fed high-salt diet. Figure 2. Effect of vehicle (V), olmesartan (O), pravastatin (P), combined olmesartan and pravastatin (O+P), and hydralazine (H) on acetylcholine-induced vascular relaxation (A), coronary arterial thickening (B), and perivascular fibrosis (C) of DS rats fed high-salt diet. A, Each plot represents mean±SEM (n=8 to 9 per group). Right top panels show representative images of light micrographs of LV coronary arterial thickening and perivascular fibrosis. Original magnification, ×200. Each bar represents mean±SEM (n=4 to 8 per group). L indicates DS rats fed low-salt diet; NS, not significant. Eiichiro Yamamoto et al. Arterioscler Thromb Vasc Biol. 2007;27: Copyright © American Heart Association, Inc. All rights reserved.

4 Figure 3. Effect of each treatment on vascular NADPH oxidase (A), p22phox (B), superoxide (C), and eNOS activity (D) of DS rats fed high-salt diet. Figure 3. Effect of each treatment on vascular NADPH oxidase (A), p22phox (B), superoxide (C), and eNOS activity (D) of DS rats fed high-salt diet. Top panels in B and C show representative Western blot and fluorescence photomicrographs, respectively, in each group. #P<0.05, *P<0.01 vs V. Each bar represents mean±SEM. A: L, n=9; V, n=9; H, n=4; O, n=9; P, n=9; O+P, n=8. B: L, n=9; V, n=9; H, n=5; O, n=9; P, n=9; O+P, n=8. C: n=5 per group. D: n=4 to 5 per group. Abbreviations are the same as Figure 2. L indicates DS rats fed low-salt diet. Eiichiro Yamamoto et al. Arterioscler Thromb Vasc Biol. 2007;27: Copyright © American Heart Association, Inc. All rights reserved.

5 Figure 4. Effect of each treatment on phospho-akt (p-akt), total akt, phospho-eNOS (p-eNOS), and total eNOS of DS rats fed high-salt diet. Figure 4. Effect of each treatment on phospho-akt (p-akt), total akt, phospho-eNOS (p-eNOS), and total eNOS of DS rats fed high-salt diet. Top panels show representative Western blot in each group. Each bar represents mean±SEM (n=5 per group). Abbreviations are the same as Figure 2. L indicates DS rats fed low-salt diet. Eiichiro Yamamoto et al. Arterioscler Thromb Vasc Biol. 2007;27: Copyright © American Heart Association, Inc. All rights reserved.

6 Figure 5. Effect of each treatment on eNOS dimer disruption (A) and DHFR protein levels (B) of DS rats fed high-salt diet. Figure 5. Effect of each treatment on eNOS dimer disruption (A) and DHFR protein levels (B) of DS rats fed high-salt diet. Top panels in A and B show representative Western blot in each group. Each bar represents mean±SEM (n=5 per group). Abbreviations are the same as Figure 2. L indicates DS rats fed low-salt diet. Eiichiro Yamamoto et al. Arterioscler Thromb Vasc Biol. 2007;27: Copyright © American Heart Association, Inc. All rights reserved.

7 Figure 6. Effect of each treatment on vascular nitrotyrosine of DS rats fed high-salt diet.
Figure 6. Effect of each treatment on vascular nitrotyrosine of DS rats fed high-salt diet. Vascular nitrotyrosine was determined by immunohistochemistry (A) and Western blot analysis (B). Each bar represents mean±SEM (n=5 per group). Abbreviations are the same as Figure 2. L indicates DS rats fed low-salt diet. Eiichiro Yamamoto et al. Arterioscler Thromb Vasc Biol. 2007;27: Copyright © American Heart Association, Inc. All rights reserved.


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