PMID- 21330937
OWN - NLM
STAT- MEDLINE
DCOM- 20110701
LR  - 20110829
IS  - 1473-5598 (Electronic)
IS  - 0263-6352 (Linking)
VI  - 29
IP  - 4
DP  - 2011 Apr
TI  - Rho kinase inhibition activates the homologous angiotensin-converting 
      enzyme-angiotensin-(1-9) axis in experimental hypertension.
PG  - 706-15
LID - 10.1097/HJH.0b013e3283440665 [doi]
AB  - BACKGROUND: Angiotensin II (Ang II) levels depend on renin, 
      angiotensin-converting enzyme (ACE), and on the homologous angiotensin-converting 
      enzyme (ACE2). Increased ACE and Ang II levels are associated with higher Rho 
      kinase activity. However, the relationship between Rho kinase activation and ACE2 
      in hypertension is unknown. OBJECTIVE: The role of the Rho kinase signaling 
      pathway in both enzymatic activity and aortic gene expression of ACE2 in 
      deoxycorticosterone acetate (DOCA) hypertensive rats was assessed in the present 
      study. METHODS AND RESULTS: Compared with sham animals, Rho kinase activity was 
      higher by 400% (P<0.05) in the aortic wall of the DOCA hypertensive rats. In 
      addition to blood pressure reduction, the specific Rho kinase inhibitor fasudil 
      reduced aortic Rho kinase activity to levels observed in the sham control group 
      and increased ACE2 enzymatic activity (by 83% in plasma and by 52% in the aortic 
      wall, P<0.05), ACE2, and endothelial nitric oxide synthase (eNOS) aortic mRNA 
      levels (by 340 and 40%, respectively, P<0.05) with respect to the untreated 
      hypertensive DOCA rats. Fasudil also increased significantly plasma levels of 
      Ang-(1-9) in normotensive and in the hypertensive rats. Aortic mRNA and protein 
      levels of transforming growth factor-beta1 (TGF-beta1), plasminogen activator inhibitor 
      1 (PAI-1), and monocyte chemoattractant protein 1 (MCP-1) were significantly 
      (P<0.05) higher in the untreated DOCA rats and were normalized by fasudil 
      administration. CONCLUSION: In experimental hypertension, Rho-associated, 
      coiled-coil containing protein kinase (ROCK) inhibition reduces blood pressure 
      and increases ACE2 levels and activity. At the same time, ROCK inhibition reduces 
      angiotensin II and increases Ang-(1-9) plasma levels. Fasudil also increases 
      vascular eNOS mRNA levels and reduces aortic overexpression of the remodeling 
      promotion proteins TGF-beta1, PAI-1, and MCP-1. This effect might additionally 
      contribute to the antihypertensive and antiremodeling effects of ROCK inhibition 
      in hypertension.
FAU - Ocaranza, Maria P
AU  - Ocaranza MP
AD  - Departamento de Enfermedades Cardiovasculares, Hospital Clinico, Facultad de 
      Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. 
      mocaran@med.puc.cl
FAU - Rivera, Paulina
AU  - Rivera P
FAU - Novoa, Ulises
AU  - Novoa U
FAU - Pinto, Melissa
AU  - Pinto M
FAU - Gonzalez, Leticia
AU  - Gonzalez L
FAU - Chiong, Mario
AU  - Chiong M
FAU - Lavandero, Sergio
AU  - Lavandero S
FAU - Jalil, Jorge E
AU  - Jalil JE
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 (Angiotensins)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
SB  - IM
CIN - J Hypertens. 2011 Aug;29(8):1660-1. PMID: 21750438
MH  - Angiotensins/blood
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Enzyme Activation
MH  - Hypertension/*metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Peptidyl-Dipeptidase A/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - rho-Associated Kinases/*antagonists & inhibitors
EDAT- 2011/02/19 06:00
MHDA- 2011/07/02 06:00
CRDT- 2011/02/19 06:00
PHST- 2011/02/19 06:00 [entrez]
PHST- 2011/02/19 06:00 [pubmed]
PHST- 2011/07/02 06:00 [medline]
AID - 10.1097/HJH.0b013e3283440665 [doi]
PST - ppublish
SO  - J Hypertens. 2011 Apr;29(4):706-15. doi: 10.1097/HJH.0b013e3283440665.