HYPOXIA-STIMULATED GLYCEROL PRODUCTION FROM THE ISOLATED, PERFUSED RAT-HEART IS MEDIATED BY NONADRENERGIC MECHANISMS

Factors controlling hypoxia induced myocardial glycerol release were s tudied in isolated, perfused rat hearts. A constant coronary flow rate 10 ml g(-1) min(-1) was maintained. The perfusion buffer was gassed w ith O-2-N-2 mixtures containing 5% CO2. The O-2:N-2 ratios were normox ia 95:0, hypoxia 30:65, and severe hypoxia 10:85 (v/v). Glycerol and l actate release were stimulated during a 30-min period of either hypoxi a or severe hypoxia but remained constant during normoxia. Tissue glyc erol-3-phosphate levels were increased after 30 min hypoxia compared w ith after a similar period of normoxic perfusion (p < 0.01) and furthe r increased after severe hypoxia (p < 0.01 vs hypoxia). beta-Adrenocep tors remained sensitive to isoprenaline during hypoxia, demonstrated b y 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 hy poxia was inhibited by both atenolol and timolol (1 x 10(-5) M). In co ntrast, beta-adrenoceptor blockade using these drugs failed to reduce glycerol release induced by either hypoxia or severe hypoxia. Both dru gs attenuated the rise in glycerol-3-phosphate during hypoxia. Chronic denervation by pretreatment with 6-hydroxydopamine reduced hypoxia-st imulated glycerol release by only 30%. Thus, a major part of hypoxia-i nduced glycerol release is mediated by non-adrenergic mechanisms. The results of this study bring into question the validity of the use of g lycerol production during hypoxia as a reliable measure of myocardial lipolysis.