PMID- 16444602
OWN - NLM
STAT- MEDLINE
DCOM- 20060418
LR  - 20211203
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 283
IP  - 1-2
DP  - 2006 Feb
TI  - Involvement of Rho-kinase in experimental vascular endothelial dysfunction.
PG  - 191-9
AB  - The present study has been designed to investigate the effect of fasudil 
      (Rho-kinase inhibitor) in diabetes mellitus (DM) and hyperhomocyteinemia (HHcy) 
      induced vascular endothelial dysfunction (VED). Streptozotocin (55 mg kg(-1), 
      i.v., once only) and methionine (1.7% w/w, p.o., daily for 4 weeks) were 
      administered to rats to produce DM (serum glucose >140 mg dl(-1)) and HHcy (serum 
      homocysteine >10 microM) respectively. VED was assessed using isolated aortic 
      ring, electron microscopy of thoracic aorta, and serum concentration of 
      nitrite/nitrate. Serum thiobarbituric acid reactive substances (TBARS) 
      concentration was estimated to assess oxidative stress. Atorvastatin has been 
      employed in the present study as standard agent to improve vascular endothelial 
      dysfunction. Fasudil (15 mg kg(-1) and 30 mg kg(-1), p.o., daily) and 
      atorvastatin (30 mg kg(-1), p.o., daily) treatments significantly attenuated 
      increase in serum glucose and homocysteine but their concentrations remained 
      markedly higher than sham control value. Fasudil and atorvastatin treatments 
      markedly prevented DM and HHcy-induced (i) attenuation of acetylcholine induced 
      endothelium-dependent relaxation, (ii) impairment of vascular endothelial lining, 
      (iii) decrease in serum nitrite/nitrate concentration, and (iv) increase in serum 
      TBARS. It may be concluded that fasudil prevented DM and HHcy-induced VED 
      partially by decreasing serum glucose and homocysteine concentration due to 
      inhibition of Rho-kinase. Moreover, inhibition of Rho-kinase by fasudil and 
      consequent prevention of oxidative stress may have directly improved VED in 
      diabetic and hyperhomocysteinemic rats. The Rho-kinase appears to be a pivotal 
      target site involved in DM and HHcy-induced VED.
FAU - Shah, Dhvanit I
AU  - Shah DI
AD  - Department of Pharmaceutical Sciences and Drug Research, Punjabi University, 
      Patiala, Punjab, India.
FAU - Singh, Manjeet
AU  - Singh M
LA  - eng
GR  - K01 DK085217/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Blood Glucose)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrroles)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 5W494URQ81 (Streptozocin)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - N9YNS0M02X (Acetylcholine)
RN  - Q0CH43PGXS (fasudil)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Antibiotics, Antineoplastic/toxicity
MH  - Aorta, Thoracic/cytology/drug effects/enzymology
MH  - Atorvastatin
MH  - Blood Glucose/drug effects/metabolism
MH  - Diabetes Complications/therapy
MH  - Diabetes Mellitus, Experimental/pathology/*therapy
MH  - Endothelium, Vascular/drug effects/*enzymology/*pathology
MH  - Heptanoic Acids/pharmacology
MH  - Homocysteine/drug effects/metabolism
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
MH  - Hyperhomocysteinemia/pathology/*therapy
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Nitrates/blood
MH  - Nitrites/blood
MH  - Oxidative Stress
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Pyrroles/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Streptozocin/toxicity
MH  - Thiobarbituric Acid Reactive Substances/metabolism
MH  - Vasodilation/drug effects
MH  - rho-Associated Kinases
EDAT- 2006/01/31 09:00
MHDA- 2006/04/19 09:00
CRDT- 2006/01/31 09:00
PHST- 2005/07/13 00:00 [received]
PHST- 2005/09/01 00:00 [accepted]
PHST- 2006/01/31 09:00 [pubmed]
PHST- 2006/04/19 09:00 [medline]
PHST- 2006/01/31 09:00 [entrez]
AID - 10.1007/s11010-006-2679-6 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2006 Feb;283(1-2):191-9. doi: 10.1007/s11010-006-2679-6.