title: Enhanced salt sensitivity following shRNA silencing of neuronal TRPV1 in rat spinal cord.
abstract: OBJECTIVE
  To investigate the effects of selective knockdown of TRPV1 channels in the lower thoracic and upper lumbar segments of spinal cord, dorsal root ganglia (DRG) and mesenteric arteries on rat blood pressure responses to high salt intake.
  
  
  METHODS
  TRPV1 short-hairpin RNA (shRNA) was delivered using intrathecal injection (6 μg · kg(-1) · d(-1), for 3 d). Levels of TRPV1 and tyrosine hydroxylase expression were determined by Western blot analysis. Systolic blood pressure and mean arterial pressure (MAP) were examined using tail-cuff and direct arterial measurement, respectively.
  
  
  RESULTS
  In rats injected with control shRNA, high-salt diet (HS) caused higher systolic blood pressure compared with normal-salt diet (NS) (HS:149 ± 4 mmHg; NS:126 ± 2 mmHg, P<0.05). Intrathecal injection of TRPV1 shRNA significantly increased the systolic blood pressure in both HS rats and NS rats (HS:169 ± 3 mmHg; NS:139 ± 2 mmHg). The increases was greater in HS rats than in NS rats (HS: 13.9% ± 1.8%; NS: 9.8 ± 0.7, P<0.05). After TRPV1 shRNA treatment, TRPV1 expression in the dorsal horn and DRG of T8-L3 segments and in mesenteric arteries was knocked down to a greater extent in HS rats compared with NS rats. Blockade of α1-adrenoceptors abolished the TRPV1 shRNA-induced pressor effects. In rats injected with TRPV1 shRNA, level of tyrosine hydroxylase in mesenteric arteries was increased to a greater extent in HS rats compared with NS rats.
  
  
  CONCLUSIONS
  Selective knockdown of TRPV1 expression in the lower thoracic and upper lumbar segments of spinal cord, DRG, and mesenteric arteries enhanced the prohypertensive effects of high salt intake, suggesting that TRPV1 channels in these sites protect against increased salt sensitivity, possibly via suppression of sympatho-excitatory responses.
authors.affiliation: Department of Medicine, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Shuang-quan
authors.initials: SQ
authors.lastname: Yu
authors.forename: Donna H
authors.initials: DH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D005727:Ganglia, Spinal / Q000378:metabolism; D020868:Gene Silencing; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013116:Spinal Cord / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D017673:Sodium Chloride, Dietary; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat