Effects of short-term exposure to noradrenaline and adrenaline on adrenoceptor responses

Adrenaline (0.05 and 1.5 mumol/kg per h) and noradrenaline (0.09 and 0.5 mumol/kg per h) were infused i.v. into conscious rabbits. Pressor responses to bolus doses of phenylephrine, alpha-methylnoradrenaline and chronotropic responses to isoprenaline were studied before and during infusion. Plasma adrenaline levels rose from 1.4 +/- 0.5 to 13 +/- 2 and 31 +/- 9 nM during the 0.05 and 1.5 mumol/kg per h infusions respectively while noradrenaline levels rose from 2.0 +/- 0.9 to 16 +/- 7 and 29 +/- 11 nM during the 0.09 and 0.5 mumol/kg per h noradrenaline infusions. Pressor responses to alpha-methylnoradrenaline were attenuated within 2.5 and 60 min during the higher and lower rates of adrenaline infusion respectively. Attenuation occurred within 10 min with the higher rate infusion of noradrenaline but no change was seen during the lower noradrenaline infusion. Chronotropic responses to isoprenaline were also reduced during the adrenaline infusions but not during noradrenaline infusion. In contrast no change was observed in phenylephrine pressor responses. These results suggest that short-term elevation in the levels of the endogenous catecholamines, noradrenaline and adrenaline, can cause desensitisation of alpha 2- and beta-adrenoceptors but not of alpha 1-adrenoceptors.