caa a22 4500 397558228 CHVBK 20180308164809.0 cr unu---uuuuu 161202e199603 xx s 000 0 eng 10.1093/oxfordjournals.jbchem.a021277 doi (NATIONALLICENCE)oxford-10.1093/oxfordjournals.jbchem.a021277 Effect of a Nitric Oxide Synthase Inhibitor, S-Ethylisothiourea, on Cultured Cells and Cardiovascular Functions of Normal and Lipopolysaccharide-Treated Rabbits [Elektronische Daten] [Han Geuk Seo, Noriko Fujiwara, Hideaki Kaneto, Michio Asahi, Junichi Fujii, Naoyuki Taniguchi] Nitric oxide (NO) is synthesized from L-arginine by three isoforms of NO synthase (NOS). It is essential to suppress the function of the inducible i so form (macNOS) for amelioration of some inflammatory diseases in which the cytotoxic effect of NO is involved. S-Ethyliso-thiourea (S-EIU) was reported to be a potent and specific inhibitor of macNOS. We also confirmed that it rather specifically inhibited the activity of the purified macNOS and the formation of nitrite by RAW264.7 cells compared to NG-monomethyl-L-arginine (L-NMA) and NG-nitro-L-arginine (l-NNA), the other isoforms being less effective. S-EIU suppressed the release of nitrite and lactate dehydrogenase from rat vascular smooth muscle cells treated with interleukin-lβ and forskolin more potently than L-NMA or L-NNA. S-EIU also slightly suppressed internucleosomal DNA cleavage in pancreatic β-cells induced by NO produced by macNOS. Intravenous administration of either S-EIU at 0.1 mg/kg/min or L-NMA at 1 mg/kg/min increased the blood pressure but decreased the heart rate in normal rabbits, while aminoguanidine at 1 mg/kg/min affected neither cardiovascular function. These inhibitors at these doses caused recovery of the blood pressure in lipopolysac-charide-treated rabbits that exhibited lowered blood pressure similar to that in the case of septic shock. Although S-EIU seemed not to be an adequate inhibitor for therapeutic use in vivo due to its side effects on cardiovascular functions, it is one of the most potent inhibitors of macNOS among reported inhibitors in vitro © by the Journal of Biochemistry Regular Papers nationallicence blood pressure nationallicence S-ethylisothiourea nationallicence nitric oxide nationallicence nitric oxide synthase nationallicence septic shock nationallicence Seo Han Geuk Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut Fujiwara Noriko Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut Kaneto Hideaki Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut Asahi Michio Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut Fujii Junichi Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut Taniguchi Naoyuki Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut The Journal of Biochemistry Oxford University Press 119/3(1996-03), 553-558 0021-924X 119:3<553 1996 119 jbchem https://doi.org/10.1093/oxfordjournals.jbchem.a021277 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/oxfordjournals.jbchem.a021277 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Seo Han Geuk Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut NATIONALLICENCE 700 1- Fujiwara Noriko Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut NATIONALLICENCE 700 1- Kaneto Hideaki Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut NATIONALLICENCE 700 1- Asahi Michio Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut NATIONALLICENCE 700 1- Fujii Junichi Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut NATIONALLICENCE 700 1- Taniguchi Naoyuki Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 119/3(1996-03), 553-558 0021-924X 119:3<553 1996 119 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford