title: Ribonucleic acid interference knockdown of interleukin 6 attenuates cold-induced hypertension.
abstract: The purpose of this study was to determine the role of the proinflammatory cytokine interleukin (IL) 6 in cold-induced hypertension. Four groups of male Sprague-Dawley rats were used (6 rats per group). After blood pressure was stabilized, 3 groups received intravenous delivery of adenoassociated virus carrying IL-6 small hairpin RNA (shRNA), adenoassociated virus carrying scrambled shRNA, and PBS, respectively, before exposure to a cold environment (5 degrees C). The last group received PBS and was kept at room temperature (25 degrees C, warm) as a control. Adenoassociated virus delivery of IL-6 shRNA significantly attenuated cold-induced elevation of systolic blood pressure and kept it at the control level for < or =7 weeks (length of the study). Chronic exposure to cold upregulated IL-6 expression in aorta, heart, and kidneys and increased macrophage and T-cell infiltration in kidneys, suggesting that cold exposure increases inflammation. IL-6 shRNA delivery abolished the cold-induced upregulation of IL-6, indicating effective silence of IL-6. Interestingly, RNA interference knockdown of IL-6 prevented cold-induced inflammation, as evidenced by a complete inhibition of tumor necrosis factor-alpha expression and leukocyte infiltration by IL-6 shRNA. RNA interference knockdown of IL-6 significantly decreased the cold-induced increase in vascular superoxide production. It is noted that IL-6 shRNA abolished the cold-induced increase in collagen deposition in the heart, suggesting that inflammation is involved in cold-induced cardiac remodeling. Cold exposure caused glomerular collapses, which could be prevented by knockdown of IL-6, suggesting an important role of inflammation in cold-induced renal damage. In conclusion, cold exposure increased IL-6 expression and inflammation, which play critical roles in the pathogenesis of cold-induced hypertension and cardiac and renal damage.
authors.affiliation: Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126-0901, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Crosswhite
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001795:Blood Pressure Determination; D003080:Cold Temperature; D016001:Confidence Intervals; D000229:Dependovirus; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011336:Probability; D012313:RNA / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013481:Superoxides; D012313:RNA
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