Attenuation of histamine-induced lymphatic smooth muscle contractility by arachidonic acid

Recent investigations have identified a class of outwardly rectifying potassium channels activated directly by arachidonic acid (AA) and select other fatty acids (FA) that inhibit smooth muscle contractions. We hypothesized that lymphatic smooth muscle contains similar fatty acid activated channels. Fresh porcine tracheobronchial lymphatic vessel rings were mounted in organ baths and connected to force-velocity transducers. Contractile responses were measured following exposure to histamine alone, with AA, and following AA washout, demonstrating a 40-55% inhibition of histamine-induced contractility by AA. Despite addition of indomethacin and nordihydroguaiaretic acid to inhibit formation of active AA metabolites, AA still attenuated contractility by 24-31%. Myristic acid and linoelaidic acid, FA's that are not substrates for cyclooxygenase or 5-lipoxygenase, inhibited histamine-induced contractility by 19 and 15%, respectively. The effects of AA and the other FA's were eliminated by exposure to a high potassium solution. The data support the existence of AA-activated hyperpolarizing potassium channels in lymphatic smooth muscle. Arachidonic acid, in addition to its metabolites, may play a direct role in regulating lymphatic smooth muscle tone.