Effect of hypoxia in mice mesenteric arteries surrounded by adipose tissue

Aim: To investigate the influence of hypoxia on the vasoactive effect of perivascular white adipose tissue. Methods: Isometric tension recordings were performed on mesenteric arteries from Swiss male mice with or without adherent adipose tissue. Results: Hypoxia (bubbling with 95% N-2, 5% CO2) induced a biphasic response, i.e. vasoconstriction followed by vasorelaxation, in pre-contracted (noradrenaline, 10 mu M) mesenteric arteries with adipose tissue in the presence of indomethacin (10 mu M) and N-omega-nitro-L-arginine (0.1 mM). Only a small vasorelaxation was observed in arteries without adipose tissue. Pre-contraction with 60 or 120 mm K+, incubation with tetraethylammoniumchloride (1 and 3 mm), apamin (1 mu M) combined with charybdotoxin (0.1 mu M) or 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) (10 mu M) significantly impaired the hypoxic vasorelaxation. Removal of the endothelium only reduced the hypoxic vasorelaxation. Apamin (1 mu M) and charybdotoxin (0.1 mu M) did not influence the vasorelaxation of sodium hydrosulfide hydrate. Zinc protoporphyrin IX (10 mu M), miconazole (10 mu M), 8-(p-sulfophenyl) theophylline (0.1 mm), 1 H-[1, 2, 4] oxadiazolo[4,3-A]quinoxalin-1-one (10 mu M), apocynin (0.3 mM), diphenyliodonium (1 mu M), catalase (2500 U mL(-1)) and tempol (0.1 mM) did not influence the hypoxic vasorelaxation. In contrast to losartan (0.1 mM), indomethacin (10 mu M) and SQ-29548 (10 mu M) significantly reduced the hypoxic vasoconstriction. Conclusions: Moderate hypoxia induces a biphasic vasomotor response in mice mesenteric arteries surrounded by adipose tissue. The hypoxic vasoconstriction is endothelium independent, whereas the vasodilation is endothelium dependent, soluble guanylyl cyclase independent and in part mediated by opening K-Ca channels. Cyclooxygenase metabolites mediate the hypoxic vasoconstriction, while endothelium-derived hyperpolarizing factor plays a small role in the hypoxic vasorelaxation.