caa a22 4500 475833813 CHVBK 20180406123848.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1023/A:1007897308187 doi (NATIONALLICENCE)springer-10.1023/A:1007897308187 Inhibition of Nitric Oxide Synthesis Induces Coronary Vascular Remodeling and Cardiac Hypertrophy Associated with the Activation of p70 S6 Kinase in Rats [Elektronische Daten] [Tetsuo Minamino, Masafumi Kitakaze, Philip Papst, Yasunori Ueda, Yasuhiko Sakata, Hiroshi Asanuma, Akiko Ogai, Tsunehiko Kuzuya, Naohiro Terada, Masatsugu Hori] Chronic inhibition of nitric oxide (NO) synthesis is reported to induce the thickening of coronary artery walls and cardiac hypertrophy in vivo via angiotensin II receptors. Increased protein synthesis is the main feature of these structural changes. Activation of 70 kD S6 kinase (p70S6K) phosphorylates the 40S ribosomal protein S6 that regulates protein synthesis. We examined the role of p70S6K in the vascular and myocardial structural changes induced by the chronic inhibition of NO synthesis. The following 5 groups were studied: untreated Wister-Kyoto rats, those treated with an inhibitor of NO synthase, N ω-nitro-L-arginine methyl ester (L-NAME), those treated with L-NAME and an angiotensin I converting enzyme inhibitor (imidapril), those treated with L-NAME and hydralazine, and those treated with L-NAME and an inhibitor of p70S6K (rapamycin). After 8 weeks, wall-to-lumen ratio in myocardium and cardiomyocyte cross-sectional areas were quantified. L-NAME increased systolic blood pressure, wall-to-lumen ratio, and cardiomyocyte cross-sectional area compared with control animals. Imidapril or rapamycin, but not hydralazine, markedly reduced these structural changes. L-NAME increased p70S6K activity in myocardium compared with control rats. Imidapril or rapamycin prevented the activation of p70S6K activity in myocardium induced by L-NAME. These results suggest that activation of p70S6K plays an important role in coronary vascular remodeling and cardiac hypertrophy induced by the chronic inhibition of nitric oxide synthesis in vivo. Kluwer Academic Publishers, 2000 rapamycin nationallicence ACE inhibitor nationallicence hydralazine nationallicence L-NAME nationallicence protein synthesis nationallicence Minamino Tetsuo Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut Kitakaze Masafumi Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut Papst Philip Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, 80206, Denver, CO, USA aut Ueda Yasunori Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut Sakata Yasuhiko Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut Asanuma Hiroshi Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut Ogai Akiko Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut Kuzuya Tsunehiko Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut Terada Naohiro Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, 80206, Denver, CO, USA aut Hori Masatsugu Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/5(2000-10-01), 533-542 0920-3206 14:5<533 2000 14 10557 https://doi.org/10.1023/A:1007897308187 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007897308187 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Minamino Tetsuo Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Kitakaze Masafumi Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Papst Philip Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, 80206, Denver, CO, USA aut NATIONALLICENCE 700 1- Ueda Yasunori Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Sakata Yasuhiko Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Asanuma Hiroshi Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Ogai Akiko Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Kuzuya Tsunehiko Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut NATIONALLICENCE 700 1- Terada Naohiro Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, 80206, Denver, CO, USA aut NATIONALLICENCE 700 1- Hori Masatsugu Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/5(2000-10-01), 533-542 0920-3206 14:5<533 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer