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Opening of the adenosine triphosphate-sensitive potassium channel attenuates cardiac remodeling induced by long-term inhibition of nitric oxide synthesis

Role of 70-kDa S6 kinase and extracellular signal-regulated kinase

Shoji Sanada, MD^*, Koichi Node, MD^*, Hiroshi Asanuma, MD^*, Hisakazu Ogita, MD^*, Seiji Takashima, MD^*, Tetsuo Minamino, MD^*, Masanori Asakura, MD^*, Yulin Liao, MD^*, Akiko Ogai, BS, Jiyoong Kim, MD, Masatsugu Hori, MD, FACC^* and Masafumi Kitakaze, MD, FACC^,*

^* Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
Cardiology Division of Medicine, National Cardiovascular Center, Suita, Japan

View larger version (25K): [in a new window]   Figure 1 Time-course changes in systolic blood pressure. See text for details. Glib = glibenclamide; Hyd = hydralazine; JTV0.3 = JTV-506 at 0.3 mg/kg per day; Ncr3 and Ncr10= nicorandil at 3 and 10 mg/kg per day, respectively; PD = PD98059; Rap = rapamycin. **p < 0.01 vs. control group.

View larger version (31K): [in a new window]   Figure 2 The left ventricular (LV) weight /body weight ratios. *p < 0.05 and **p < 0.01 vs. control group. p < 0.05 and p < 0.01 vs. L-NAME group. Abbreviations as in Figure 1.

View larger version (128K): [in a new window]   Figure 3 Representative histologic findings of myocytes (A) and myocyte cross-sectional areas (B). *p < 0.05 and **p < 0.01 vs. control group. p < 0.05, p < 0.01 vs. L-NAME group. 1 = control group; 2 = L-NAME treatment; 3 = D-NAME treatment; 4 = L-NAME + Hyd treatment; 5 = L-NAME + JTV treatment; 6 = L-NAME + Ncr3 treatment; 7 = L-NAME + Ncr10 treatment; 8 = L-NAME + Rap treatment; 9 = L-NAME + PD treatment; 10 = Glib treatment; 11 = L-NAME + Glib treatment; and 12 = L-NAME + Ncr10 + Glib treatment. Abbreviations as in Figure 1.

View larger version (24K): [in a new window]   Figure 4 Activity of P70S6K (A) and ERK (B) in myocardial tissue. See text for details. **p < 0.01 vs. control group. p < 0.05 and p < 0.01 vs. L-NAME group. Abbreviations as in Figure 1.