Send to

Choose Destination
Int J Tissue React. 2000;22(4):93-100.

Inhibition of NF kappa B activation by pyrrolidine dithiocarbamate prevents in vivo hypoxia/reoxygenation-mediated myocardial angiogenesis.

Author information

Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut, USA.


This study sought to examine the effect of nonlethal moderate whole body hypoxic challenge (10% 02/90% N2) on rat myocardial angiogenesis. Sprague Dawley rats were subjected to 4 h of systemic normobaric hypoxemic hypoxia (10 +/- 0.4% O2) in an anesthesia chamber or to 4 h of normoxia (ambient 20.9 +/- 0.4% O2) to time-match the duration of hypoxia. All rats were then kept under normoxic conditions. Rats were sacrificed and hearts harvested either after 2 h for subsequent electrophoretic mobility gel shift assay for NF kappa B, or after 24 h for subsequent Western blot analysis for vascular endothelial growth factor (VEGF) and after 7 days for immunohistochemistry for capillary density measurement. We also used pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF kappa B, before 1 h of hypoxia to establish the possible role of NF kappa B in modulating myocardial angiogenesis. The results showed significant induction of VEGF protein expression after 4 h of hypoxia followed by 24 h of reoxygenation in the rat myocardium. The DNA binding activity of NF kappa B was increased compared with the hypoxic group. However inhibition of NF kappa B by PDTC decreased capillary density significantly when compared with the hypoxic group. These findings demonstrate the role of NF kappa B and VEGF in myocardial angiogenesis for the first time.

[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center