Hypoxia enhances the relaxing influence of perivascular adipose tissue in isolated mice aorta

Adipose tissue releases an adipocyte-derived relaxing factor (ADRF) lowering tone of isolated arteries. The potential influence of hypoxia on the vasorelaxing properties of adipose tissue was investigated. Aortas from male Swiss mice with or without adherent adipose tissue were mounted in a wire myograph for isometric tension recording. Hypoxia (bubbling with 95% N-2, 5% CO2) relaxed precontracted (norephinephrine, 5 mu M) aorta with adipose tissue while only a minimal vasorelaxing effect was observed in arteries without adipose tissue. This effect was also seen after precontraction with prostaglandin F-2 alpha (30 mu M) or U-46619 (10 nM). Precontraction with 60 or 120 mM K+, incubation with tetraethylammoniumchloride (3 mM) or glibenclamide (30 mu M) significantly impaired the hypoxic response. Glibenclamide (30 mu M) enhanced the vasorelaxing effect of NaHS (except at high concentrations of NaHS). Lactate (10 nM to 1 mM) had no effect on preparations with or without adipose tissue. 8-(p-sulfophenyl)theophylline (0.1 mM), zinc protoporphyrin IX (10 mu M), 1 H-[1, 2, 4]oxadiazolo[4,3-A]quinoxalin-1-one (10 mu M) and removal of the endothelium did not influence the hypoxic relaxation. Our findings indicate that hypoxia has a relaxing influence on mice aorta that is dependent on the presence of adherent adipose tissue. This relaxation is partly mediated by opening K-ATP channels and independent of the endothelium and soluble guanylyl cyclase. Neither lactate, adenosine, CO nor H2S seems to be involved in this hypoxic response. However, the involvement of the as yet unidentified adipocyte-derived relaxing factor (ADRF) cannot be excluded. (C) 2010 Elsevier B.V. All rights reserved.