Dual effects of histamine on spontaneous activity in isolated bovine mesenteric lymphatics

The mode of action of histamine on spontaneous contractions is isolated bovine mesenteric lymphatics was investigated by recording isometric tensions. Histamine at lower concentrations between about 5 x 10(-8) and 10(-6) M caused a dose-dependent deceleration of the rhythm of spontaneous contractions. Higher concentrations of histamine (more than about 5 x 10(-6) M) produced a dose-related acceleration of the rhythm in association with a slight elevation of basal tone in 115 of 173 preparations. In 58 of 173 lymphatic preparations, histamine at concentrations ranging from about 5 x 10(-8) to 10(-5) M caused only the positive chronotropic effect. The histamine-induced positive and negative chronotropic effects were unaltered by pretreatment with alpha- and beta-adrenergic antagonists but were dose-dependently antagonized by pretreatment with H1- or H2-blockers (diphenhydramine or cimetidine). The specific H1- and H2-agonists, 2-pyridylethylamine (2PEA) and dimaprit caused dose-related positive and negative chronotropic effects, respectively, on spontaneous contractions of isolated bovine mesenteric lymphatics. The effect of 2PEA was significantly blocked by pretreatment with 10(-6) M diphenhydramine, whereas the effect of dimaprit was suppressed by 10(-6) M cimetidine. These results suggest that both H1- and H2-receptors are located on the plasma membrane of smooth muscle cells in bovine mesenteric lymphatics, and that the excitations of H1- and H2-receptors respectively produce an acceleration and a deceleration of the rhythm of spontaneous contractions in lymphatic smooth muscles.