Interaction of histaminergic drugs with adrenergic neurotransmission in rabbit ear central artery

The interaction of histamine and other histaminergic agents with adrenergic neurotransmission in blood vessels was studied in vitro. The experiments were carried out on ear central arteries isolated from male Chinchilla rabbits. The proximal segment of the artery was perfused with Krebs-Henseleit solution at a rate of 3.0 ml/min and was allowed a 120-min adaptation before the experiments. Contractions of the arterial smooth muscle were evoked either by noradrenaline (NA) or by low-frequency electrical stimulation (LFES). The effects of histamine and the other histaminergic agents on the arterial tone and on the NA- or LFES-induced contractions were studied. When applied extralumenally in concentrations higher than 1 x 10(-12) M histamine and 2-(2-aminoethyl) thiazole (2-AET) enhanced the LFES-induced smooth-muscle contractions. Dimaprit (DMP) did not markedly change the LFES-contractile effects. Diphenhydramine (DPH) and mepyramine (MEP) in higher concentrations potentiated the contractions in response to LFES. Ranitidine (RAN) moderately potentiated and cimetidine (CIM) did not affect the LFES-evoked contractions of the artery. None of the drugs tested significantly changed the NA-induced contractions. The results only partly confirm the assumption that histamine exerts its modulatory effects on adrenergic neurotransmission via postsynaptic excitatory H1-receptors and presynaptic inhibitory H2-receptors.