Hypoxic Contraction of Isolated Rabbit Mesenteric Veins: Contribution of Endothelium and Attenuation by Volatile Anesthetics

Background: Acute systemic hypoxia induces mesenteric venoconstriction in intact rabbits in part because of an increase in chemoreflex-mediated sympathetic efferent nerve activity. Inhaled anesthetics attenuate this reflex response. The direct effects of hypoxia on mesenteric veins are unknown. The purpose of the current study was to examine the effects of hypoxia on isolated rabbit mesenteric capacitance veins and to determine the effects of halothane, isoflurane, and enflurane on the responses to hypoxia.

Methods: Isometric tension was measured before, during, and after 10 min of hypoxia in the rings of either quiescent or norepinephrine contracted veins, with or without endothelium. Effects of various pharmacologic agents and volatile anesthetics on the responses to hypoxia were examined.

Results: Hypoxia augmented contractions to norepinephrine and phenylephrine only in endothelium-intact veins. The hypoxic response was inhibited by phentolamine (alpha-adrenoceptor antagonist) and abolished in the absence of extracellular Calcium2+. There were no effects of propranolol (beta-adrenoceptor antagonist), ryanodine (a sarcoplasmic reticulum Calcium2+ depleter), indomethacin (cyclooxygenase inhibitor), or nordihydrogualaretic acid (lipoxygenase inhibitor), L-NAME an inhibitor of nitric oxide synthase) enhanced basal sensitivity of veins to norepinephrine but had no effect on the response to hypoxia. Nicardipine (a blocker of voltage-gated calcium channels) depressed the hypoxic contraction by 86 plus/minus 5%, phosphoramidon (an inhibitor of endothelin-converting enzyme) by 82 plus/minus 8%, and BQ-123 (a specific endothelin-1 receptor antagonist) by 47 + 10%. Volatile anesthetics (1.0 MAC) inhibited responses to hypoxia in the absence as well as presence of L-NAME.