This study further investigates the mechanisms responsible for the effects of acute and severe
hypoxia, and subsequent reoxygenation, on the contractility of isolated rat mesenteric arteries. In
noradrenaline (NA)-contracted arteries,
hypoxia caused a relaxation to near baseline levels. Reoxygenation resulted in an immediate transient contraction before tension returned more slowly to prehypoxia levels. Similar responses to
hypoxia were observed in tissues precontracted by addition of KCl (60 mM) or
U46619 (10 microM); however, the transient contraction upon reoxygenation was absent (KCl) or reduced (
U46619). Responses to
hypoxia were independent of changes in intracellular
calcium ([Ca2+]i), while those to reoxygenation were accompanied by corresponding changes in [Ca2+]i and were completely abolished by
ryanodine. In NA-contracted tissues, all responses were unaffected by endothelial removal or by inhibitors of
nitric oxide synthase and
cyclooxygenase. The K+ channel blockers
triethylamine (
TEA),
glibenclamide, and
4-aminopyridine (4-AP) had no effect on the responses to
hypoxia. The transient contractile response to reoxygenation was, however, significantly reduced in the presence of 4-AP. The response to reoxygenation, but not that to
hypoxia, was inhibited by the
antioxidant dithiothreitol (DTT) and the
NAD(P)H-oxidase inhibitor
diphenyliodonium (DPI). These data suggest that hypoxic vasodilation occurs independently of reductions in [Ca2+]i. Alternatively, transient contractions on reoxygenation are dependent upon the generation of
reactive oxygen species and the release of stored Ca2+.