Effects of adrenoceptor blockade on plasma catecholamine levels during adrenaline infusion

1. The present experiments investigate the effects of phenoxybenzamine and propranolol, singly and in combination, on plasma catecholamine levels in sheep receiving a three-hour adrenaline infusion. 2. Five groups of five anaesthetized sheep were studied for a period of 3 h each. One group acted as a control and received only a saline (0.9% w/v NaCl solution) infusion. A second group received a constant infusion of adrenaline (2 mug kg body weight-1 min-1). A third group received a similar adrenaline infusion, having been premedicated with phenoxybenzamine (1 mg/kg body weight). A fourth group recieved a similar adrenaline infusion following premedication with (+/-)-propranolol hydrochloride (7 mug/kg body weight). The fifth group received the adrenaline infusion following premedication with both the alpha- and beta-blocker in the above doses. 3. Plasma catecholamines were measured on blood samples taken at seven intervals before during and following the infusion. 4. Control animals receiving only a saline infusion remained physiologically and biochemically stable throughout the experimental period. 5. Adrenaline infusion in animals not receiving adrenoceptor blocking drugs caused a rise in plasma adrenaline levels from a low basal value of 1 mug/litre to a maximum level of 19.8 mug/litre. Animals premedicated with phenoxybenzamine exhibited a similar response. 6. Animals premedicated with propranolol before the infusion of adrenaline did not demonstrate as marked a rise of plasma adrenaline levels as the two previous groups. The maximum mean plasma adrenaline level recorded in this group was 6.88 mug/litre. 7. Animals premedicated with phenoxybenzamine and propranolol before the infusion of adrenaline showed only a small rise in plasma adrenaline levels compared with animals receiving adrenaline infusion alone. The maximum mean plasma adrenaline level in the group was only 3.43 mug/litre. 8. The studies demonstrate that by an unknown mechanism beta-adrenoceptor blockade with (+/-)-propranolol, either alone or in combination with phenoxybenzamine, lowers the plasma adrenaline response evoked by adrenaline infusion.