Adrenaline Activation of Prejunctional β-Adrenoceptors and Hypertension

Abstract

Rats implanted with osmotic minipumps containing adrenaline (0.2 ml, 2.9 mM) developed increased systolic and diastolic blood pressures, whereas blood pressures in rats implanted with osmotic minipumps containing the same amount of noradrenaline did not differ from those of sham-operated control rats. Heart rates did not differ from control in either treatment group. Concomitant administration of metoprolol (2.5 mg/kg, i.p., twice daily) abolished the effect of adrenaline-treatment on blood pressure. Plasma concentrations of adrenaline and noradrenaline released from the minipumps were 17 nM and 2.4 nM, respectively The atria accumulated 56 pmol/g of adrenaline released from the minipump. In isolated atria, adrenaline (10 nM) increased noradrenergic transmitter release by acting on prejunctional beta-adrenoceptors. Incubation of isolated atria with adrenaline led to the accumulation of 46 pmol/g. This adrenaline was released as a cotransmitter and mediated a positive feedback effect on transmission which was disrupted by metoprolol (0.1 micro M). It is suggested that the increase in blood pressure produced in rats by chronic treatment with adrenaline is due to facilitation of noradrenergic transmission to cardiovascular effector tissues. Such an effect may be involved in the development of stress-induced hypertension.