Exogenous nitric oxide inhibits Rho-associated kinase activity in patients with angina pectoris: a randomized controlled trial.
The RhoA/Rho-associated kinase (ROCK) pathway has a key physiological role in the pathogenesis of atherosclerosis. Increased ROCK activity is associated with cardiovascular diseases. Endogenous nitric oxide (NO) has an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in patients with angina pectoris. This is a prospective, open-label, randomized, controlled study. A total of 30 patients with angina pectoris were randomly assigned to receive 40 mg day(-1) of isosorbide mononitrate (n=15, 12 men and 3 women, mean age of 63±12 years, isosorbide mononitrate group) or conventional treatment (n=15, 13 men and 2 women, mean age of 64±13 years, control group) for 12 weeks. ROCK activity in peripheral leukocytes was measured by western blot analysis. ROCK activities at 4 and 12 weeks after treatment were decreased in the isosorbide mononitrate group (0.82±0.33 at 0 week, 0.62±0.20 at 4 weeks, 0.61±0.19 at 12 weeks, n=15 in each group, P<0.05, respectively) but not altered in the control group. ROCK1 and ROCK2 expression levels were similar in all treatment periods in the two groups. These findings suggest that the administration of exogenous NO can inhibit ROCK activity, indicating that the usage of exogenous NO could have a protective effect in patients with angina pectoris.
Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Tatsuya
T
Maruhashi
Department of Regeneration and Medicine, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Hiroshima University, Hiroshima, Japan.
Kensuke
K
Noma
Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Noritaka
N
Fujimura
Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Masato
M
Kajikawa
Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Takeshi
T
Matsumoto
Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Takayuki
T
Hidaka
Department of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
Ayumu
A
Nakashima
Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Yasuki
Y
Kihara
Section of Cardiology, University of Chicago Medical Center, Chicago, IL, USA.
James K
JK
Liao
Department of Regeneration and Medicine, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Hiroshima University, Hiroshima, Japan.
Yukihito
Y
Higashi
D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000201:enzymology*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy; D015415:Biomarkers; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D011446:Prospective Studies; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D015415:Biomarkers; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate