Article

Altered endothelial Ca2+ regulation after ischemia/reperfusion produces potentiated endothelium-derived hyperpolarizing factor-mediated dilations.

Department of Anesthesiology, Baylor College of Medicine, Houston, Tex 77030, USA.
Stroke (impact factor: 5.73). 10/2002; 33(9):2285-91. pp.2285-91
Source: PubMed

ABSTRACT Endothelium-derived hyperpolarizing factor (EDHF)-mediated dilations are potentiated after several pathologies, including ischemia/reperfusion (I/R). However, no study to date has addressed the mechanism by which this potentiation occurs. This study tested the hypothesis that potentiated EDHF-mediated dilations are due to altered endothelial Ca2+ handling after I/R.
Rat middle cerebral arteries (MCAs) were isolated after 2 hours of MCA occlusion and 24 hours of reperfusion (or sham surgery). This model has been previously demonstrated to produce potentiated EDHF-mediated dilations. MCAs were studied in a pressurized/perfused vessel chamber equipped for the simultaneous measurement of endothelial Ca2+ (with fura 2) and artery diameter. Measures were made after luminal administration of UTP (P2Y2 purinoceptor agonist), 2 MeS-ATP (P2Y1 purinoceptor agonist), and Br-A23187 (receptor-independent Ca2+ ionophore) for sham and I/R MCAs.
I/R resulted in significantly potentiated UTP-mediated dilations (through a P2Y2 purinoceptor) and endothelial Ca2+ responses in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin. Endothelial Ca2+ and diameter responses were also significantly potentiated with 2 MeS-ATP (through a P2Y1 purinoceptor) when L-NAME and indomethacin were absent. Br-A23187, a receptor-independent Ca2+ ionophore, produced significantly potentiated endothelial Ca2+ responses after I/R in the presence of L-NAME/indomethacin. Evaluation of artery diameter as a function of endothelial Ca2+ demonstrated no differences between sham and I/R groups.
These findings demonstrate that I/R results in augmented endothelial Ca2+ responses that appear to be downstream of the receptor level. Moreover, these data suggest that this augmented Ca2+ response contributes to the potentiated EDHF-mediated dilations after I/R.

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    Article: Vascular hypoxic preconditioning relies on TRPV4-dependent calcium influx and proper intercellular gap junctions communication.
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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

augmented Ca2+ response contributes
 
augmented endothelial Ca2+ responses
 
endothelial Ca2+ handling
 
endothelial Ca2+ responses
 
Endothelium-derived hyperpolarizing factor
 
fura 2
 
I/R MCAs
 
luminal administration
 
N(G)-nitro-L-arginine methyl ester
 
P2Y1 purinoceptor
 
P2Y1 purinoceptor agonist
 
P2Y2 purinoceptor
 
P2Y2 purinoceptor agonist
 
potentiated EDHF-mediated dilations
 
potentiated endothelial Ca2+ responses
 
pressurized/perfused vessel chamber
 
Rat middle cerebral arteries
 
receptor level
 
receptor-independent Ca2+ ionophore
 
simultaneous measurement
 

Sean P Marrelli