Evidence against inhibition of sarcoplasmic reticulum Ca2+-pump as mechanism of H2O2-induced contraction of rat aorta.
Acta Pharmacol Sin
; 22(6): 498-504, 2001 Jun.
Article
in En
| MEDLINE
| ID: mdl-11747754
ABSTRACT
AIM:
To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+-pump is involved in H2O2-induced contraction of endothelium-denuded rat aorta.METHODS:
Isometric tension recording of H2O2 and cyclopiazonic acid (CPA)-induced contractions of rat aortic rings were compared in the absence or presence of various pharmacological tools to discriminate their signaling pathways involved.RESULTS:
Both H2O2 and CPA contracted rat aortic rings, but with different contractile patterns. H2O2 triggered a fast and phasic contraction, whereas CPA elicited a slow and sustained contraction. In Ca2+-free medium, pretreatment of aortic rings with CPA 30 micromol/L but not with H2O2 30 micromol/L nearly abolished phenylephrine (10 micromol/L)-induced contraction. In addition, upon the maximal contraction induced by thapsigargin 30 micromol/L, H2O2 but not CPA further contracted aortic rings. On the other hand, H2O2 (30 micromol/L)- but not CPA (10 micromol/L)-induced contraction could be inhibited by suramin and RB-2 (each 100 micromol/L), two P2-purinoceptor antagonists. Furthermore, although pretreatment with 2-APB, a membrane permeable IP3 receptor blocker, inhibited both H2O2- and CPA-induced contractions, only H2O2 (30 micromol/L)-induced contraction could be depressed, to different degree, by various inhibitors of receptor-coupled or downstream signaling enzymes, including PLC, PKC, PLA2, COX, and protein tyrosine kinases.CONCLUSION:
Inhibition of smooth muscle SR Ca2+-pump is unlikely the mechanism responsible for H2O2-induced contraction of endothelium-denuded rat aorta.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcoplasmic Reticulum
/
Ca(2/) Mg(2/)-ATPase
/
Hydrogen Peroxide
/
Indoles
/
Muscle Contraction
Limits:
Animals
Language:
En
Journal:
Acta Pharmacol Sin
Journal subject:
FARMACOLOGIA
Year:
2001
Document type:
Article
Affiliation country:
China
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA