title: Chronic restraint stress aggravated arthritic joint swell of rats through regulating nitric oxide production.
abstract: Stress-related hormone norepinephrine (NE) displayed diverse effects on immune system including macrophages, which influenced many kinds of inflammatory diseases. Nitric oxide (NO) from activated macrophages played an important role in inflammatory diseases. In this study, we investigated under chronic restraint stress how NE influenced the joint swell of Complete Freund's Adjuvant (CFA)-induced arthritis of rats and whether NE regulated macrophage's production of NO through influencing phosphorylation of protein kinases C (PKC). The results showed chronic restraint stress exacerbated paw swell of rats with arthritis. Inhibitor of inducible nitric oxide synthase, S-methylisothiourea (SMT), and 6-hydroxydopamine (6-OHDA) could counteract the effect of restraint stress on arthritis. NE, NO and endotoxin in plasma of rats underwent restraint were improved significantly. In vitro experiments, NE could promote macrophage to produce more NO and iNOS when macrophage was activated by lipopolysaccharide (LPS). This effect could be inhibited by α adrenergic antagonist phentolamine. Nevertheless, through α receptor NE could promote the phosphorylation of PKC and PKC inhibitor staurosporine could counteract NE's enhancive effect on production of NO and iNOS of macrophages. This study revealed that NE could exacerbate arthritic joint swell through promoting NO production, which was in α receptor dependent way through enhancing phosphorylation of PKC for NE to enhance the iNOS expression of activated macrophage.
authors: Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, PR China.
authors: Yan-Fei
authors: YF
authors: Mao
authors: You-Lei
authors: YL
authors: Zhang
authors: Qi-Hong
authors: QH
authors: Yu
authors: Yao-Hao
authors: YH
authors: Jiang
authors: Xin-Wei
authors: XW
authors: Wang
authors: Yuan
authors: Y
authors: Yao
authors: Jun-Long
authors: JL
authors: Huang
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology; D005620:Freund's Adjuvant; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D012149:Restraint, Physical / Q000009:adverse effects*; D013564:Sympathetic Nervous System / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D009569:Nitric Oxide; D005620:Freund's Adjuvant; D052247:Nitric Oxide Synthase Type II; D011493:Protein Kinase C; D009638:Norepinephrine; D010646:Phentolamine