Interaction between presynaptic facilitatory angiotensin II receptors and inhibitory muscarinic cholinoceptors on 3H-noradrenaline release in the rabbit heart

Abstract

The existence of a functional interaction between presynaptic receptors modulating the release of noradrenaline was studied in the rabbit heart. Isolated right atria were prelabelled with 3H-noradrenaline and the overflow of tritium was induced by field stimulation (2 Hz, 0.1 ms duration, supramaximal voltage for a total of 180 pulses). In atria superfused with Krebs' solution containing 10 mumol/l cocaine and 30 mumol/l corticosterone, angiotensin II (10 nmol/l) increased the stimulation-evoked overflow of 3H-transmitter by 2.8-fold. The addition of atropine (0.3 mumol/l) to the perfusion medium, either in the presence or in the absence of uptake inhibitors, further enhanced the facilitatory effect of angiotensin II (3H-transmitter release increased by 3.5-fold). Exposure to 1 mumol/l carbachol decreased by 65% the stimulation-evoked release of 3H-transmitter while the facilitatory effect of angiotensin II determined in the presence of the muscarinic cholinoceptor agonist was enhanced (3H-transmitter release increased by 6.6-fold). Conversely, during sustained activation of presynaptic angiotensin receptors producing a 2.5-fold increase in the release of 3H-transmitter, the inhibitory effect of carbachol remained unchanged. These results suggest a functional interaction between presynaptic inhibitory muscarinic cholinoceptors and the presynaptic facilitatory angiotensin receptor which modulate the release of noradrenaline from cardiac noradrenergic nerves.