Functional role of cardiac presynaptic alpha 2-adrenoreceptors in the bradycardia of alpha-adrenoreceptor agonists in pentobarbitone-and urethane-anaesthetized normotensive rats.

Abstract

The relative potencies of 6 α‐adrenoreceptor agonists, with differing physicochemical properties, at cardiac presynaptic α‐adrenoreceptors were determined by measuring their ability to reduce the tachycardia produced by stimulation of the cardiac sympathetic nerves in pithed rats. The compounds studied were clonidine, B‐HT 933 (azepexole), oxymetazoline, St 91, naphazoline and DPI. The bradycardia produced by the same compounds in bilaterally vagotomized, urethane‐ or pento‐barbitone‐anaesthetized normotensive rats were also compared. The relative order of presynaptic potency appeared similar to that observed for the bradycardic activity of the compounds in urethane‐ and pento‐barbitone‐anaesthetized rats. In pentobarbitone‐anaesthetized rats all compounds evoked a maximal effect of 18–20% reduction in heart rate. In urethane‐anaesthetized rats, however, a difference was observed between clonidine and azepexole on the one hand and oxymetazoline, St 91, naphazoline and DPI on the other hand. The former induced a 20–22% reduction in cardiac frequency, whereas the latter diminished heart rate by 10–16% only. In vagotomized, bilaterally adrenalectomized, urethane‐anaesthetized rats, clonidine, St 91, naphazoline and azepexole evoked a 25% reduction in heart rate, whereas a 20% reduction was observed for DPI and oxymetazoline. A radio‐enzymatic determination of plasma catecholamines demonstrated that under urethane‐anaesthesia plasma adrenaline concentrations were significantly elevated over the values observed in pentobarbitone‐anaesthetized rats. This rise in plasma adrenaline was related to the amount of urethane used. In urethane‐anaesthetized, bilaterally adrenalectomized rats, plasma adrenaline was not significantly elevated. These findings demonstrate the involvement of cardiac presynaptic α2‐adrenoreceptors in the acute bradycardia, evoked by the α‐adrenoreceptor agonist upon intravenous application to pentobarbitone‐anaesthetized, normotensive rats. In urethane‐anaesthetized rats, however, the functional role of the cardiac presynaptic α2‐adrenoreceptors may be obscured as a result of the high plasma adrenaline levels observed in these animals.