HETEROGENEITY OF TRACHEOBRONCHIAL LYMPHATIC SMOOTH MUSCLE RESPONSE TO HISTAMINE AND 5-HYDROXYTRYPTAMINE

MK Ferguson, UE Williams, AR Leff, RW Mithchell

Abstract


We assessed the responsiveness of tracheobronchial lymphatic smooth muscle to mediators of inflammation to determine whether homogeneous responses to histamine and 5-hydroxytryptamine (5-HT) are demonstrated among species typically used in studies of lymph vessels. Fresh porcine and bovine tracheobronchial lymph vessels were suspended from force-displacement transducers in baths containing oxygenated Krebs solution. Concentration-response curves were generated by cumulative addition of histamine (10(-7) to 10(-3) M) or 5-HT (10(-7) to 3 x 10(-4) M). Active tension (AT) was expressed in milligrams and as a percentage of initial vessel ring response to 65mM KCl. Histamine elicited concentration-dependent contraction, yielding maximum AT in porcine rings of 1116 +/- 127 mg (n = 39; 129.1 +/- 10.5% of KCl response) and in bovine rings of 733 +/- 106 mg (n = 20; 65.8 +/- 12.9%; P = 0.0005 for percent responses). PD2 values (negative log10 of the concentration at half-maximum effect) were 4.49 +/- 0.08 and 4.82 +/- 0.08; (P = 0.0034). 5-HT elicited concentration-dependent contraction, yielding maximum AT of 560 +/- 50 mg in porcine rings (n = 15; 97.2 +/- 9.7%) and 2892 +/- 454 mg in bovine rings (n = 27; 159.0 +/- 29%; P < 0.0001 for percent responses). PD2 values were 6.25 +/- 0.05 and 5.28 +/- 0.04 (P < 0.0001). The data demonstrate a role for inflammatory mediators in the modulation of tracheobronchial lymphatic smooth muscle tone that is species- and mediator-specific, and support the potential for paracrine regulation of tracheobronchial lymph flow.

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