Effects of histamine on the contractile and electrical activity in isolated lymphatic vessels of the guinea‐pig mesentery

The effect of histamine on the rate of lymphatic vessel constrictions and lymphatic smooth muscle membrane potential was examined in the guinea‐pig mesentery. Histamine (0.01–5 μ M ) increased the frequency and decreased the amplitude of constrictions in lymphatic vessels under intraluminal perfusion. This response was accompanied by a depolarization of the smooth muscle membrane potential, an increase in the activity of spontaneous transient depolarizations (STDs), the proposed pacemaker for constrictions in these vessels, and an increase in the occurrence of action potentials. Responses to histamine were inhibited by the H 1 receptor antagonist pyrilamine (0.2 μ M ), but unaffected by NO synthase inhibition with N G ‐nitro L ‐arginine ( L ‐NOARG, 100 μ M ) and lysis of the endothelium. In about 50% of the vessels, a decrease in constriction frequency, STD activity and a smooth muscle hyperpolarization were observed in response to dimaprit (10 μ M ), suggesting the presence of H 2 receptors. These vessels had also a significantly lower basal contractile rate. Lymphatic vessel pumping was not affected by R‐α‐methylhistamine (10–50 μ M ), ruling out a role for H 3 receptor stimulation in the histamine response. The present results suggest a direct action of histamine on the lymphatic smooth muscle via stimulation of H 1 (and in some vessels H 2 ) receptors. H 1 receptors enhance and H 2 receptors slow down lymphatic pumping, the dominant effect being an increased contractile activity. Correlation of these effects with histamine‐induced changes in membrane potential and STD activity suggests the involvement of these electrical changes in the initiation of the contractile response.British Journal of Pharmacology (2002) 136 , 1210–1218. doi: 10.1038/sj.bjp.0704820