Receptor mechanisms of bradykinin-mediated activation of prenodal lymphatic smooth muscle

We have previously shown that several endogenous vasoactive agents constrict prenodal lymph vessels in the canine forelimb. In this study, we assessed the receptor mechanisms by which bradykinin activates lymphatic smooth muscle. Intralymphatic (i.l.) infusion of bradykinin at concentrations of 3.82 x 10(-6), 3.82 x 10(-5) and 3.82 x 10(-4) molar significantly increased lymphatic perfusion pressure. To determine the potential role of lymphatic alpha-receptors in this response, we infused bradykinin at a concentration of 3.82 x 10(-4) molar i.l. before and during intra-arterial (i.a.) phentolamine administration. Prior to phentolamine, bradykinin resulted in a doubling of the lymphatic perfusion pressure. Phentolamine alone had no effect on the resting lymphatic pressure, but significantly reduced forelimb arterial pressures. When the infusion of bradykinin was repeated during phentolamine administration, there was no significant change in the lymphatic perfusion pressure. To determine the subclass of alpha-adrenergic receptors involved in this response, we infused bradykinin and the alpha1-receptor agonist phenylephrine i.l. before and during administration of i.a. prazosin, a specific alpha1-receptor antagonist, i.a. Prior to prazosin, both phenylephrine and bradykinin significantly increased lymphatic perfusion pressure. During prazosin administration, neither phenylephrine nor bradykinin significantly altered the lymphatic perfusion pressure. These data indicate that bradykinin-mediated increases in prenodal lymphatic smooth muscle tone are mediated by lymphatic alpha1-adrenergic receptors.