Contractile responses of isolated rat mesenteric arteries to acute episodes of severe hypoxia and subsequent reoxygenation.

Abstract:

: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+.

journal_name

Microvasc Res

journal_title

Microvascular research

authors

Bruce J,Taggart M,Austin C

doi

10.1016/j.mvr.2004.08.001

keywords:

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

303-12

issue

3

eissn

0026-2862

issn

1095-9319

pii

S0026-2862(04)00113-X

journal_volume

68

pub_type

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