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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1880    most recent 01319.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sun, Z. Articles by Wang, X. Search for Related Content PubMed PubMed Citation Articles by Sun, Z. Articles by Wang, X.

RNAi inhibition of mineralocorticoid receptors prevents the development of cold-induced hypertension

¹Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and ²Departments of Medicine and Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, Florida

Submitted 11 November 2007 ; accepted in final form 21 February 2008

The objective was to determine whether the mineralocorticoid receptor (MR) plays a role in the initiation and development of cold-induced hypertension (CIH) by testing the hypothesis that the RNA interference (RNAi) inhibition of the MR attenuates CIH. The recombinant adeno-associated virus (AAV) carrying a short-hairpin small-interference RNA for MR (MRshRNA) or a scrambled sequence (ControlshRNA) was constructed. Six groups of albino mice were used (6 mice/group). Three groups were exposed to cold (6.7°C), whereas the remaining three groups were kept at room temperature (RT; warm) as controls. In each temperature condition, three groups received an intravenous injection of MRshRNA, ControlshRNA, or virus-free PBS, respectively, before exposure to cold. The viral complexes (0.35 x 10¹¹ particles/mouse, 0.5 ml) or PBS (0.5 ml) was delivered into the circulation via the tail vein. The blood pressure (BP) of the mice treated with ControlshRNA or PBS increased significantly during exposure to cold, whereas the BP of the cold-exposed MRshRNA-treated mice did not increase and remained at the level of the control group kept at RT. Thus AAV delivery of MRshRNA prevented the initiation of CIH. MRshRNA significantly attenuated cardiac and renal hypertrophy. MRshRNA decreased the cold-induced increase in MR protein expression to the control level in the hypothalamus, kidneys, and heart, indicating an effective prevention of the cold-induced upregulation of MR. RNAi inhibition of MR resulted in significant decreases in the plasma level of norepinephrine, plasma renin activity, and plasma level of aldosterone in cold-exposed mice. MR played a critical role in the initiation and development of CIH. AAV delivery of MRshRNA may serve as a new approach for the prevention of cold-induced hypertension.

short-hairpin RNA; aldosterone; blood pressure; adeno-associated virus; cardiac hypertrophy; RNA interference