Adrenergic regulation of the acute ischaemic myocardium: facts, interpretations and consequences.
Anoxic stress is accompanied by activation of the central and peripheral sympathetic nervous system resulting in a high local catecholamine concentration. The authors studied how myocardial cells cope with the high level of catecholamines under ischaemic conditions. The beta-adrenoceptor-adenylate cyclase system (AC) was investigated in different models of ischaemia and anoxia (global ischaemia, low-perfused hearts, coronary artery ligation) in rat hearts. It was shown that beta-receptor function is not changed up to 40 min of ischaemia. Myocardial AC function was depressed in the total ischaemic myocardium but not in the low-perfused hearts indicating a non-uniform alteration of AC function. Reduced AC activity was completely reversible by aerobic perfusion as long as the ischaemic period did not exceed 20 min. Depression of AC function during severe ischaemia was avoided by reducing Ca2+ in the extracellular fluid and by pretreatment with Ca2+ channel blockers (verapamil). Depression of AC function during severe ischaemia is caused mainly by increased intracellular Ca2+ which inhibits AC at its catalytic site. Myocardial ischaemia alters the response of myocardial cells to catecholamines and other activators of the AC system. This alteration is time-limited and turns damage to AC function from reversible to irreversible after prolongation of ischaemia to more than 30 min.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D007545:Isoproterenol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine