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The mode of action of bradykinin (BK) on bovine mesenteric lymphatics was investigated by recording isometric tensions and action potentials in the isolated longitudinal segments. Addition of BK in concentrations from 10(-10) to 4 X 10(-6) M caused dose-related tonic contractions. BK in a low concentration accelerated the rhythm of action potential discharges in the spontaneously beating preparations and elicited frequent discharges of action potentials and a rapid rise in smooth muscle tone associated with phasic contractions. BK in high concentrations (more than 10(-7) M) caused a further rise of tension in the preparations which had already been depolarized in a high-K solution. The contraction induced by 4 X 10(-9) M-BK in the standard solution was abolished in a Ca-free environment or in the presence of a Ca-antagonist, 10(-4) M-D-600, though more than 50% of the contraction caused by 10(-6) M-BK still remained in both circumstances. In a Ca-free solution containing 1 mM-EGTA (Ca-free standard solution), 10(-6) M-BK caused a slight contraction even after high-K-induced contractions were completely blocked. The contractile response to 10(-6) M-BK in the Ca-free standard solution was augmented after activation of beta-receptors. It is concluded that the BK-induced contractions may be closely related to an increased Ca influx through the membrane and release of membrane-bound and intracellular Ca. The increased uptake of Ca into the BK-sensitive intracellular store may contribute to the relaxing effect of beta-agonist.

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