PMID- 17198912
OWN - NLM
STAT- MEDLINE
DCOM- 20070315
LR  - 20131121
IS  - 0895-7061 (Print)
IS  - 0895-7061 (Linking)
VI  - 20
IP  - 1
DP  - 2007 Jan
TI  - Involvement of Ras-regulated myosin light chain phosphorylation in the captopril 
      effects in spontaneously hypertensive rats.
PG  - 53-61
AB  - BACKGROUND: Early treatment with captopril prevents the development of 
      hypertension by inhibiting the generation of angiotensin II and smooth muscle 
      contraction. Although smooth muscle contraction is regulated by myosin light 
      chain phosphorylation (MLC-P), the role of MLC-P in captopril effects in 
      hypertension has not been described. Therefore, we treated spontaneously 
      hypertensive rats (SHR) with captopril and investigated the effects of this agent 
      on downstream signaling. METHODS: Male SHR (n = 12) were treated with captopril 
      (3.7 mmol/L in drinking water) beginning in utero and continuing up to 12 weeks 
      of age. Age- and sex-matched untreated SHR and Wistar-Kyoto (WKY) rats were used 
      as controls. Rats were split into three subgroups and were sacrificed at 12, 18, 
      or 24 weeks of age. Systolic blood pressure, left ventricular weight, and body 
      weight were measured. Mesenteric arteries were removed for histologic and 
      biochemical studies. RESULTS: At 12 weeks, captopril significantly decreased 
      systolic blood pressure (from 198 +/- 10 to 125+/-16 mm Hg), reduced left 
      ventricular weight-to-body weight ratios (from 2.94 +/- 0.06 to 2.17 +/- 0.08 
      mg/g), and prevented vascular remodeling in mesenteric arteries in SHR. Ras 
      expression, extracellular receptor kinase phosphorylation (ERK-P), myosin light 
      chain kinase (MLCK) expression, and MLC-P were all significantly increased in 
      mesenteric arteries in untreated SHR compared with WKY rats. Early captopril 
      treatment in SHR significantly inhibited Ras and MLCK expression at all ages and 
      decreased ERK-P and MLC-P at 12 and 18 weeks in mesenteric arteries. CONCLUSIONS: 
      These data demonstrate that the antihypertensive effects of captopril are 
      correlated with inhibition of Ras-regulated ERK activation, MLCK expression, and 
      MLC-P.
FAU - Hu, Wen-Yang
AU  - Hu WY
AD  - Department of Physiology and Biophysics, College of Medicine, University of 
      Illinois at Chicago, Chicago, IL, USA.
FAU - Han, Yoo-Jeong
AU  - Han YJ
FAU - Gu, Lian-Zhi
AU  - Gu LZ
FAU - Piano, Mariann
AU  - Piano M
FAU - de Lanerolle, Primal
AU  - de Lanerolle P
LA  - eng
GR  - NIH 59618/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Am J Hypertens
JT  - American journal of hypertension
JID - 8803676
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Myosin Light Chains)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9G64RSX1XD (Captopril)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Angiotensin-Converting Enzyme Inhibitors/therapeutic use
MH  - Animals
MH  - Captopril/therapeutic use
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Female
MH  - Hypertension/drug therapy/*metabolism
MH  - Hypertrophy, Left Ventricular/prevention & control
MH  - Male
MH  - Mesenteric Arteries/metabolism
MH  - Myosin Light Chains/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Inbred SHR
MH  - ras Proteins/*metabolism
EDAT- 2007/01/03 09:00
MHDA- 2007/03/16 09:00
CRDT- 2007/01/03 09:00
PHST- 2006/03/23 00:00 [received]
PHST- 2006/05/30 00:00 [revised]
PHST- 2006/05/30 00:00 [accepted]
PHST- 2007/01/03 09:00 [pubmed]
PHST- 2007/03/16 09:00 [medline]
PHST- 2007/01/03 09:00 [entrez]
AID - S0895-7061(06)00363-3 [pii]
AID - 10.1016/j.amjhyper.2006.05.024 [doi]
PST - ppublish
SO  - Am J Hypertens. 2007 Jan;20(1):53-61. doi: 10.1016/j.amjhyper.2006.05.024.