title: Enhancement of receptor-operated cation current and TRPC6 expression in arterial smooth muscle cells of deoxycorticosterone acetate-salt hypertensive rats.
abstract: OBJECTIVE
  In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, altered reactivity of blood vessels to vasoactive agonists is frequently associated with an elevation in blood pressure. Canonical transient receptor potential (TRPC) channels are believed to encode receptor-operated cation channels (ROC), the activation of which is involved in smooth muscle depolarization and vasoconstriction. The aims of the present study were to investigate whether the ROC current is increased in DOCA-hypertensive rats and determine whether aldosterone directly enhances the expression of TRPC.
  
  
  METHODS
  The nystatin-perforated patch-clamp technique was used for the recording of receptor-stimulated ion currents in mesenteric arterial smooth muscle cells, which were enzymatically dispersed from sham-operated and DOCA-salt hypertensive rats. Expressions of TRPCs were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Western blot analysis.
  
  
  RESULTS
  Receptor-stimulated currents activated by 5-hydroxytryptamine (serotonin) and norepinephrine were increased significantly in the mesenteric arterial smooth muscle cells of DOCA-salt hypertensive rats compared to sham-operated rats. Ion-substitution experiments revealed that the enhanced currents were cation currents (ROC currents). Enhanced expression of TRPC6 in mesenteric arteries from DOCA-salt hypertensive rats was demonstrated by real-time RT-PCR. Up-regulation of TRPC6 by aldosterone treatment in vitro was also observed in A7r5 cells by RT-PCR and in western blots.
  
  
  CONCLUSIONS
  These results suggest that aldosterone enhances TRPC6 expression and ROC currents in vascular smooth muscle cells, and that this may in turn contribute to altered vascular reactivity and to hypertension.
authors.affiliation: Artificial Muscle Research Center, Departments of Physiology, College of Medicine, Konkuk University, Choongju, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Bae
authors.forename: Aeran
authors.initials: A
authors.lastname: Kim
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Wonchung
authors.initials: W
authors.lastname: Lim
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Noh
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Kim
authors.forename: Junghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Tae-Kyung
authors.initials: TK
authors.lastname: Kim
authors.forename: Sang Woong
authors.initials: SW
authors.lastname: Park
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Cho
authors.forename: Duk-Kyung
authors.initials: DK
authors.lastname: Kim
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D001158:Arteries / Q000166:cytology*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D015220:Calcium Channels / Q000096:biosynthesis* / Q000187:drug effects*; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017538:Mesenteric Artery, Superior / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000096:biosynthesis* / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D018490:Serotonin Agents; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D014662:Vasoconstrictor Agents; D012701:Serotonin; D003900:Desoxycorticosterone; D000450:Aldosterone; D009638:Norepinephrine