PMID- 15361768
OWN - NLM
STAT- MEDLINE
DCOM- 20050131
LR  - 20220309
IS  - 0263-6352 (Print)
IS  - 0263-6352 (Linking)
VI  - 22
IP  - 10
DP  - 2004 Oct
TI  - Rho kinase and PAI-1 in Bartter's/Gitelman's syndromes: relationship to 
      angiotensin II signaling.
PG  - 1963-9
AB  - OBJECTIVE: Angiotensin II (Ang II)-mediated activation of Rho kinase (ROK) is 
      involved in the pathophysiology of hypertension and cardiovascular remodeling. 
      ROK also controls plasminogen activator inhibitor-1 (PAI-1) which promotes 
      vascular fibrosis contributing to atherogenesis. Bartter's and Gitelman's 
      syndromes (BS/GS) are useful models to investigate abnormalities of vascular tone 
      regulation, due to their reduced short- and long-term signaling pathways of Ang 
      II. This study evaluated, using BS/GS as a model, ROK and PAI-1 gene and protein 
      expression and the effect of Ang II co-incubation on ROK and PAI-1 gene and 
      protein expression. DESIGN, METHODS AND RESULTS: We measured ROK and PAI-1 gene 
      and protein expression [reverse transcription-polymerase chain reaction (RT-PCR) 
      and Western blot] in mononuclear cells (PBM) from one BS and eight GS patients. 
      The effect of Ang II on ROK and PAI-1 gene and protein expression was also 
      evaluated and compared with 10 controls. ROK gene and protein expression was 
      reduced in BS/GS [0.47 +/- 0.11 densitometric units (d.u.) versus 0.70 +/- 0.04 
      d.u., P = 0.0038 and 0.39 +/- 0.07 d.u. versus 0.55 +/- 0.07 d.u., P = 0.0026, 
      respectively]. The basal level of PAI-1 gene and protein expression did not 
      differ (0.40 +/- 0.03 d.u. versus 0.39 +/- 0.02 d.u. and 0.81 +/- 0.02 d.u. 
      versus 0.83 +/- 0.02 d.u., respectively). Ang II increased ROK and PAI-1 gene and 
      protein expression only in controls: from 0.70 +/- 0.04 to 0.90 +/- 0.06 d.u., P 
      = 0.007 (ROK mRNA); from 0.55 +/- 0.07 to 0.86 +/- 0.07 d.u., P = 0.0005 (ROK 
      protein); from 0.40 +/- 0.02 to 0.63 +/- 0.03 d.u., P = 0.001 (PAI-1 mRNA); and 
      from 0.83 +/- 0.02 to 1.34 +/- 0.16 d.u., P = 0.0023 (PAI-1 protein). 
      CONCLUSIONS: This study confirms BS/GS as a human model to investigate 
      interrelated systems involved in the pathophysiology of hypertension and throws 
      more light on the cellular mechanisms of BS/GS reduced Ang II short- and 
      long-term signaling pathways.
FAU - Pagnin, Elisa
AU  - Pagnin E
AD  - Department of Clinical and Experimental Medicine, Clinica Medica 4, University of 
      Padova, Italy.
FAU - Davis, Paul A
AU  - Davis PA
FAU - Sartori, Michelangelo
AU  - Sartori M
FAU - Semplicini, Andrea
AU  - Semplicini A
FAU - Pessina, Achille C
AU  - Pessina AC
FAU - Calo, Lorenzo A
AU  - Calo LA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (RNA, Messenger)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Adult
MH  - Angiotensin II/*metabolism/pharmacology
MH  - Bartter Syndrome/*metabolism
MH  - Case-Control Studies
MH  - Female
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Kidney Diseases/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Plasminogen Activator Inhibitor 1/genetics/*metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - *Signal Transduction
MH  - Syndrome
MH  - rho-Associated Kinases
EDAT- 2004/09/14 05:00
MHDA- 2005/02/03 09:00
CRDT- 2004/09/14 05:00
PHST- 2004/09/14 05:00 [pubmed]
PHST- 2005/02/03 09:00 [medline]
PHST- 2004/09/14 05:00 [entrez]
AID - 00004872-200410000-00019 [pii]
AID - 10.1097/00004872-200410000-00019 [doi]
PST - ppublish
SO  - J Hypertens. 2004 Oct;22(10):1963-9. doi: 10.1097/00004872-200410000-00019.