1. Previous studies have shown that LD 3098 (cirazoline), a potent directly acting α-adrenoreceptor agonist, failed to antagonize heart rate increases induced by ansa subclavia stimulation in anaesthetized dogs. However, in the isolated perfused cat spleen LD 3098 inhibited transmitter release elicited by nerve stimulation and behaved as a preferential presynaptic α-adrenoreceptor agonist.
2. LD 3098 (0·01–10 μmol/l) increased the twitch response of the isolated rat vas deferens to field stimulation. However, preincubation of the tissue with prazosin (0·1 μmol/l) unmasked a presynaptic inhibitory effect of LD 3098, which was antagonized by yohimbine.
3. LD 3098 was a full agonist in isolated dog saphenous veins and in low concentrations (0·01 μmol/l) shifted the concentration—response curves to noradrenaline, potasium (K+) and prostaglandin F2α (PGF2α) to the left without changing the maximum response. Furthermore the potentiating effect of LD 3098 on PGF2α responses was antagonized by prazosin (0·1 μmol/l).
4. It is concluded that LD 3098 produces a non-specific sensitization of vascular smooth muscle by acting on postsynaptic α-adrenoreceptors.
5. This increase in end-organ sensitivity might explain why LD 3098 appears as an α-adrenoreceptor agonist with preferential affinity for postsynaptic receptors when end-organ responses to nerve stimulation are measured and yet it is a preferential presynaptic agonist in 3H-labelled transmitter-release studies. Such findings further emphasize the need for caution when assessing presynaptic activity indirectly via end-organ response to nerve stimulation.