PMID- 19371338
OWN - NLM
STAT- MEDLINE
DCOM- 20091015
LR  - 20211020
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 157
IP  - 4
DP  - 2009 Jun
TI  - Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries 
      from rats with hyperhomocysteinemia.
PG  - 568-80
LID - 10.1111/j.1476-5381.2009.00165.x [doi]
AB  - BACKGROUND AND PURPOSE: There are interactions between endothelin-1 (ET-1) and 
      endothelial vascular injury in hyperhomocysteinemia (HHcy), but the underlying 
      mechanisms are poorly understood. Here we evaluated the effects of HHcy on the 
      endothelin system in rat carotid arteries. EXPERIMENTAL APPROACH: Vascular 
      reactivity to ET-1 and ET(A) and ET(B) receptor antagonists was assessed in rings 
      of carotid arteries from normal rats and those with HHcy. ET(A) and ET(B) 
      receptor expression was assessed by mRNA (RT-PCR), immunohistochemistry and 
      binding of [(125)I]-ET-1. KEY RESULTS: HHcy enhanced ET-1-induced contractions of 
      carotid rings with intact endothelium. Selective antagonism of ET(A) or ET(B) 
      receptors produced concentration-dependent rightward displacements of ET-1 
      concentration response curves. Antagonism of ET(A) but not of ET(B) receptors 
      abolished enhancement in HHcy tissues. ET(A) and ET(B) receptor gene expressions 
      were not up-regulated. ET(A) receptor expression in the arterial media was higher 
      in HHcy arteries. Contractions to big ET-1 served as indicators of 
      endothelin-converting enzyme activity, which was decreased by HHcy, without 
      reduction of ET-1 levels. ET-1-induced Rho-kinase activity, calcium release and 
      influx were increased by HHcy. Pre-treatment with indomethacin reversed enhanced 
      responses to ET-1 in HHcy tissues, which were reduced also by a thromboxane A(2) 
      receptor antagonist. Induced relaxation was reduced by BQ788, absent in 
      endothelium-denuded arteries and was decreased in HHcy due to reduced 
      bioavailability of NO. CONCLUSIONS AND IMPLICATIONS: Increased ET(A) receptor 
      density plays a fundamental role in endothelial injury induced by HHcy. ET-1 
      activation of ET(A) receptors in HHcy changed the balance between 
      endothelium-derived relaxing and contracting factors, favouring enhanced 
      contractility.
FAU - de Andrade, C R
AU  - de Andrade CR
AD  - Department of Pharmacology, School of Medicine of Ribeirao Preto, University of 
      Sao Paulo, Ribeirao Preto, SP, Brazil.
FAU - Leite, P F
AU  - Leite PF
FAU - Montezano, A C
AU  - Montezano AC
FAU - Casolari, D A
AU  - Casolari DA
FAU - Yogi, A
AU  - Yogi A
FAU - Tostes, R C
AU  - Tostes RC
FAU - Haddad, R
AU  - Haddad R
FAU - Eberlin, M N
AU  - Eberlin MN
FAU - Laurindo, F R M
AU  - Laurindo FR
FAU - de Souza, H P
AU  - de Souza HP
FAU - Correa, F M A
AU  - Correa FM
FAU - de Oliveira, A M
AU  - de Oliveira AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090409
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Endothelin A Receptor Antagonists)
RN  - 0 (Endothelin B Receptor Antagonists)
RN  - 0 (Endothelin-1)
RN  - 0 (Nitrogen Oxides)
RN  - 0 (Receptor, Endothelin A)
RN  - 0 (Receptor, Endothelin B)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.71 (Endothelin-Converting Enzymes)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Aspartic Acid Endopeptidases/metabolism
MH  - Calcium/pharmacology
MH  - Carotid Arteries/drug effects/metabolism/*physiopathology
MH  - Dose-Response Relationship, Drug
MH  - Endothelin A Receptor Antagonists
MH  - Endothelin B Receptor Antagonists
MH  - Endothelin-1/biosynthesis/*physiology
MH  - Endothelin-Converting Enzymes
MH  - Endothelium, Vascular/drug effects/metabolism/*physiopathology
MH  - Hyperhomocysteinemia/*metabolism/*physiopathology
MH  - In Vitro Techniques
MH  - Male
MH  - Metalloendopeptidases/metabolism
MH  - Nitrogen Oxides/metabolism/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Endothelin A/biosynthesis
MH  - Receptor, Endothelin B/agonists/biosynthesis
MH  - Vasoconstriction/drug effects/physiology
MH  - Vasodilation/drug effects/physiology
PMC - PMC2707970
EDAT- 2009/04/18 09:00
MHDA- 2009/10/16 06:00
PMCR- 2010/06/01
CRDT- 2009/04/18 09:00
PHST- 2009/04/18 09:00 [entrez]
PHST- 2009/04/18 09:00 [pubmed]
PHST- 2009/10/16 06:00 [medline]
PHST- 2010/06/01 00:00 [pmc-release]
AID - BPH165 [pii]
AID - 10.1111/j.1476-5381.2009.00165.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2009 Jun;157(4):568-80. doi: 10.1111/j.1476-5381.2009.00165.x. 
      Epub 2009 Apr 9.