CO-RELEASED ADRENALINE MARKEDLY FACILITATES NORADRENALINE OVERFLOW THROUGH PREJUNCTIONAL BETA(2)-ADRENOCEPTORS DURING SWIMMING EXERCISE

The effect of intravenously applied (-)adrenaline, taken up by and rel eased from sympathetic nerves, on swimming exercise-induced noradrenal ine overflow in permanently cannulated adrenal demedullated rats was s tudied. Adrenaline (100 ng/min) was infused for 2 h, during which a pl asma concentration of 500 pg/ml (approximately 2.5 nM) was reached. On e hour later plasma adrenaline had returned to undetectable levels. Du ring swimming, adrenaline was released into the plasma in concentratio ns up to 133 pg/ml and the noradrenaline concentration was markedly en hanced as well. The total catecholamine increase amounted to 178% of c ontrol (saline infusion) in the first 3 min of swimming and 165% for t he whole 20 min. Cocaine (2.5 mg/kg plus 0.05 mg/kg/min), infused toge ther with adrenaline and continued throughout the experiment, prevente d the exercise-induced release of adrenaline and no increase in plasma noradrenaline concentration was observed. Yohimbine (0.25 mg/kg) stro ngly further enhanced the exercise-induced overflow of both noradrenal ine and adrenaline. This further increase was completely blocked by th e selective beta(2)-adrenoceptor antagonist ICI 118,551 /-)-1-[(2,3-di hydro-7-methyl-1H-inden-4-yl)oxy]-3- [(1 -methylethyl)amino]-2-butanol ) (1.0 mg/kg). These results demonstrate that adrenaline can be taken up by sympathetic nerve endings through cocaine-sensitive uptake carri ers and is released from these nerves during swimming exercise. Neuron ally released adrenaline markedly enhances exercise-induced catecholam ine overflow through activation of prejunctional beta(2)-adrenoceptors .