The effect of beta-adrenoceptor blockade on the response to hypovolaemic stress in sheep
Gilbert, C.H.; Wood, W.G.; Galton, D.J.
Journal of Pharmacy and Pharmacology 29(7): 440-442
1977
ISSN/ISBN: 0022-3573 PMID: 19586 Document Number: 122224
The reactions to controlled blood loss in sheep on the secretion and action of catecholamines were examined by measuring the changes in plasma concentrations of adrenaline AMP and free fatty acids as an index of catecholamine action. The ability of .beta.-adrenoceptor blockade to reverse the stress reactions to hypovolemia in response to graded hemorrhage was also examined. The reactions to such stress are generally considered to be due to the secretion of catecholamines which leads to tachycardia, blood vessel constriction in the skin, elevation of blood pressure and mobilization of oxidative fuels (fatty acids and glucose) by activation of lipolysis and glycogenolysis. The main metabolic effects of catecholamines are mediated by cAMP produced by the activation of a membrane bound enzyme, adenylate cyclase, found in many tissues such as liver, adipose tissue and muscle. Some of the circulatory manifestations of stress can be reduced by .beta.-adrenoceptor blockade suggesting that they are in fact produced by catecholamines. Tachycardia due to hypotension was abolished in animals treated with propranolol and practolol but animals treated with butoxamine showed no fall in heart rate during the stress. This partially supports the view that butoxamine has a primarily .beta.2-blocking effect (extracardiac) although in these animals the pulse rate did not rise as it did in untreated animals. Only some of the metabolic reactions to hypovolemic shock could be inhibited with .beta.-adrenoceptor blockade. The rise in plasma fatty acids during some periods of hypotension was prevented in sheep treated with .beta.-adrenoceptor blocking agents. Receptor blockade had very little effect on the rise in plasma cAMP throughout this period. Although catecholamines stimulate adenylate, cyclase in these tissues, there are other hormones which also activate adenylate cyclase in different tissues. High plasma concentrations of ACTH may not only activate adenylate cyclase in the adrenal cortex but also have extra-adrenal effects in adipose tissue. Although part of the metabolic reactions to stress may be mediated by cAMP such reactions are unlikely to be reduced by .beta.-adrenoceptor blockade alone if glucagon (and possibly ACTH) are also secreted. Apparently, .beta.-adrenoceptor blockade alone could not reverse the metabolic reactions to severe stress.