Critical role of exogenous nitric oxide in ROCK activity in vascular smooth muscle cells

• Published in: PloS one 2014-10, Vol.9 (10), p.e109017-e109017
• Main Authors: Maruhashi, Tatsuya, Noma, Kensuke, Iwamoto, Yumiko, Iwamoto, Akimichi, Oda, Nozomu, Kajikawa, Masato, Matsumoto, Takeshi, Hidaka, Takayuki, Kihara, Yasuki, Chayama, Kazuaki, Nakashima, Ayumu, Goto, Chikara, Liao, James K, Higashi, Yukihito
• Format: Article
• Language: English
• Subjects: Analysis; Angina pectoris; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Angiotensins; Animals; Aorta; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; Apoptosis; Arteriosclerosis; Atherosclerosis; Biology and Life Sciences; Boyden chamber; Cell growth; Cell migration; Cell Movement - drug effects; Cell Movement - physiology; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cells, Cultured; Contraction; Coronary vessels; Endothelium; Genomes; Health sciences; Heart rate; Humans; Hypertension; In vitro methods and tests; In vivo methods and tests; Kinases; Medicine; Medicine and Health Sciences; Mice; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscles; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Nitrates; Nitric oxide; Nitric Oxide - metabolism; Nitroprusside; Nitroprusside - pharmacology; Pathogenesis; Physiology; Proteins; Quantitative analysis; Rho-associated kinase; rho-Associated Kinases - metabolism; Rodents; Signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology; Signaling; Smooth muscle; Sodium; Sodium nitroprusside; University graduates
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109017

Rho-associated kinase (ROCK) signaling pathway has been shown to mediate various cellular functions including cell proliferation, migration, adhesion, apoptosis, and contraction, all of which may be involved in pathogenesis of atherosclerosis. Endogenous nitric oxide (NO) is well known to have 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 vascular smooth muscle cells (VSMCs) in vitro and in vivo. VSMCs migration was evaluated using a modified Boyden chamber assay. ROCK activities were measured by Western blot analysis in murine and human VSMCs and aorta of mice treated with or without angiotensin II (Ang II) and/or sodium nitroprusside (SNP), an NO donor. Co-treatment with SNP inhibited the Ang II-induced cell migration and increases in ROCK activity in murine and human VSMCs. Similarly, the increased ROCK activity 2 weeks after Ang II infusion in the mouse aorta was substantially inhibited by subcutaneous injection of SNP. These findings suggest that administration of exogenous NO can inhibit ROCK activity in VSMCs in vitro and in vivo.