Pronounced facilitation of endogenous noradrenaline release by presynaptic β2-adrenoceptors in the vasculature of freely moving rats

The facilitation of the noradrenaline (NA) overflow by stimulation of the presynaptic beta-adrenoceptor of the rat portal vein was investigated, using the freely moving unanesthetized permanently cannulated rat as a model. The beta 2-selective agonist fenoterol caused a maximal enhancement of about 300% of the basal NA level at a dose of 0.5 mg/kg. Following administration of cocaine (2.5 mg/kg plus 0.05 mg/kg/min) basal NA levels increased to 150% whereas combination of cocaine and fenoterol results in a dose dependant rise up to over 560% of the basal level (at a fenoterol dosage of 0.5 mg/kg). Blockade of the alpha 2-adrenoceptors with yohimbine (0.5 mg/kg) which enhances the NA level to 486%, followed by 0.125 mg/kg fenoterol results in a further 2.53-fold rise to more than 1,200% of the basal level, indicating the pronounced counterregulatory role of the presynaptic alpha 2-adrenoceptor. After ganglionic blockade with hexamethonium (3 mg/kg plus 6 mg/kg/h) the effect of yohimbine (0.5 mg/kg) alone was diminished to 162%, but the additional facilitatory effect of 0.125 mg/kg fenoterol still was 1.82-fold, to 294% of the basal level. Combination of cocaine (2.5 mg/kg plus 0.05 mg/kg/min), yohimbine (0.5 mg/kg) and fenoterol (0.125 mg/kg) induced a rise to over 9,000 pg/ml NA (about 40-fold of the basal NA level). During electrical stimulation (2 Hz, 3 ms, 5 mA) of the local portal vein nervous plexus, the role of the inhibitory alpha 2-adrenoceptor becomes even more pronounced