Hypoxia-stimulated glycerol production from the isolated, perfused rat heart is mediated by non-adrenergic mechanisms

Summary

Factors controlling hypoxia-induced myocardial glycerol release were studied in isolated, perfused rat hearts. A constant coronary flow rate 10 ml g⁻¹ min⁻¹ was maintained. The perfusion buffer was gassed with O₂−N₂ mixtures containing 5% CO₂. The O₂∶N₂ ratios were normoxia 95∶0, hypoxia 30∶65, and severe hypoxia 10∶85 (v/v). Glycerol and lactate release were stimulated during a 30-min period of either hypoxia or severe hypoxia but remained constant during normoxia. Tissue glycerol-3-phosphate levels were increased after 30 min hypoxia compard with after a similar period of normoxic perfusion (p<0.01) and further increased after severe hypoxia (p<0.01 vs hypoxia). β-Adrenoceptors remained sensitive to isoprenaline during hypoxia, demonstrated by an increase in glycerol release over a 30-min period of isoprenaline infusion from 897±317 to 1771±307 nmol g⁻¹ wet weight (p<0.05). The isoprenaline-induced increase in glycerol release during hypoxia was inhibited by both atenolol and timolol (1×10⁻⁵M). In contrast, β-adrenoceptor blockade using these drugs failed to reduce glycerol release induced by either hypoxia or severe hypoxia. Both drugs attenuated the rise in glycerol-3-phosphate during hypoxia. Chronic denervation by pretreatment with 6-hydroxydopamine reduced hypoxia-stimulated glycerol release by only 30%. Thus, a major part of hypoxia-induced glycerol release is mediated by non-adrenergic mechanisms. The results of this study bring into question the validity of the use of glycerol production during hypoxia as a reliable measure of myocardial lipolysis.