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Effect of ANG II on endothelial cell apoptosis and survival and its impact on skeletal muscle angiogenesis after electrical stimulation. Am J Physiol Heart Circ Physiol 2008 Jun;294(6):H2814-21 PMID: 18441208 PMCID: PMC2579789

Abstract

We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation is significantly attenuated when SS-13BN/Mcwi rats are fed a high-salt diet. This effect was associated with a large increase in endothelial cell (EC) apoptosis. We hypothesized that the low levels of ANG II during high-salt diet would increase EC apoptosis and consequently diminish the angiogenic response. To test this hypothesis, a series of in vitro and in vivo studies was performed. EC apoptosis and viability were evaluated after incubation with ANG II under serum-free conditions. After 24 h of incubation, ANG II increased EC viability and Bcl-2-to-Bax ratio along with a dose-dependent decrease in EC apoptosis. This effect was blocked by the ANG II type 1 receptor antagonist losartan. To confirm our in vitro results, ANG II (3 ng.kg(-1).min(-1)) was chronically infused in rats fed a high-salt diet (4% NaCl). ANG II decreased EC apoptosis and produced a significant increase (40%) in skeletal muscle angiogenesis after electrical stimulation. These in vivo results were in agreement with our in vitro results and demonstrate that the attenuation of ANG II levels during a high-salt diet may induce EC apoptosis and consequently block the angiogenic response induced by electrical stimulation. Furthermore, under normal conditions, ANG II increases EC viability and protects EC from apoptosis possibly by inactivation of the mitochondrial apoptotic pathway.

Author List

de Resende MM, Greene AS

Author

Andrew S. Greene PhD Interim Vice Chair, Chief, Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Animals
Apoptosis
Cell Proliferation
Cell Survival
Cells, Cultured
Electric Stimulation
Endothelial Cells
Infusions, Intravenous
Losartan
Mitochondria
Muscle, Skeletal
Neovascularization, Physiologic
Proto-Oncogene Proteins c-bcl-2
Rats
Rats, Inbred Strains
Sodium Chloride, Dietary
bcl-2-Associated X Protein



View this publication's entry at the Pubmed website PMID: 18441208
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