Abstract 17633: Erythropoeitin Rescues Perivascular Adipose Function Which is Lost Following Hypoxia Through Endothelium Dependent Mechanisms
Erythropoietin (EPO) has a number of effects which may be beneficial in the treatment of inflammatory diseases including type 2 diabetes and obesity. We hypothesise erythropoietin can restore normal anticontractile function of adipose tissue in small resistance arteries which is lost following hypoxia through a NOS dependent pathway Methods Wire myography was used to study mesenteric arterial segments (∼250μM) with and without intact adipose tissue from healthy male wistar rats. The effect of EPO (10u/ml) was assessed following 1 hour preincubation before experimental hypoxia (2.5 hours, 95% N2/5%CO2) and throughout hypoxia. Some arteries were denuded mechanically to determine the involvement of the endothelium in mediating the effects of EPO; this was reconfirmed in arteries with intact endothelium which were incubated with L-NNA (1mM) during the final 30 minutes of hypoxia. Contractile responses to norepinephrine were calculated as a percentage of KCl contraction and expressed as mean±SEM. Data were analysed using 2-way ANOVA, P<0.05 was considered significant.
Results: Arteries with intact adipose tissue had an increase in contractility following hypoxia compared with arteries under normoxic conditions (P=0.0067, n=12). EPO incubation throughout hypoxia partially restored the anticontractile function of adipose tissue (P=0.0004, n=8). 1 hour preincubation with EPO also part reversed the effects of hypoxia, although not significantly (P=0.0503, n=5). Arteries without adipose tissue demonstrated reduction in contractility following EPO incubation (P=0.046, n=8). Denuded arteries and incubation of intact arteries with L-NNA during hypoxia + EPO, however, were associated with responses similar to hypoxia suggesting a reduction in the beneficial effects of EPO (Denudation: P=NS, n=3; L-NNA: P=NS, n=3).
Conclusions: EPO partially rescues the loss of anticontractile effect associated with hypoxia, however, this effect seems to be associated with actions independent of the adipose tissue as arteries without surrounding adipose tissue have a reduced contractile response following incubation with EPO during hypoxia. Our data suggest that EPO is working through an endothelium dependent pathway involving NOS.
- © 2010 by American Heart Association, Inc.