Objective: Acute myocardial ischaemia has been shown to modulate the b-adrenergic system and to activate protein kinase C. The aim of this study was to investigate if two important components of ischaemia, i.e. energy depletion or acidosis, may contribute to these Ž . changes. Methods: Isolated rat hearts were perfused either with anoxia in the absence of oxygen or with cyanide in the absence of glucose as models of energy depletion with a loss of high energy phosphates. Alternatively, isolated

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... hearts were perfused with acidic modified Krebs-Henseleit solution to induce acidosis. Results: Energy depletion induced by cyanide perfusion leads to an increase of Ž . b-adrenergic receptors 81 " 7 vs. 50 " 3 fmolrmg protein, p F 0.05 comparable to the changes observed in ischaemia, yet without any change of total adenylyl cyclase activity or protein kinase C activity. Similar, yet less pronounced changes were induced by anoxic perfusion. Acidic perfusion, in contrast, promotes a translocation of protein kinase C to the plasma membranes, suggesting its rapid Ž activation. Additionally, an increased total forskolin-stimulated activity of adenylyl cyclase 515 " 16 vs. 428 " 17 pmolrminrmg, . p F 0.05 was observed. Both were comparable to the sensitization observed in early ischaemia. In acidosis, the density of b-adrenergic receptors remained unaltered. Conclusions: These data suggest that the regulation of cardiac b-adrenergic receptors is susceptible to energy depletion, but not to acidosis, whereas the intracellular enzymes both adenylyl cyclase and protein kinase C may be regulated by intracellular acidosis. This is the first differentiation of distinct components of ischaemia modulating the b-adrenergic signal transduction pathway. Both components may be operative in concert in acute myocardial ischaemia and may contribute to the regulation of these components of signal transduction observed in acute ischaemia. q