Hypoxia-stimulated glycerol production from the isolated, perfused rat heart is mediated by non-adrenergic mechanisms.
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 compared with after a similar period of normoxic perfusion (p < 0.01) and further increased after severe hypoxia (p < 0.01 vs hypoxia). beta-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 x 10(-5) M). In contrast, beta-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.
Department of Clinical Biochemistry, University of Manchester, Salford, United Kingdom.
C A
CA
Wardle
R A
RA
Riemersma
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D003326:Coronary Circulation; D003714:Denervation; D005990:Glycerol / Q000378:metabolism*; D005994:Glycerophosphates / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D000860:Hypoxia; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
D005994:Glycerophosphates; D007773:Lactates; D014280:Triglycerides; D001262:Atenolol; D016627:Oxidopamine; C029620:alpha-glycerophosphoric acid; D007545:Isoproterenol; D005990:Glycerol