The inhibitory effect of aspirin on lymphatic contractility

Abstract

Spontaneous contractions and those elicited by two different methods of electrical stimulation were studied in isolated segments of bovine mesenteric lymphatic vessels. The effect of aspirin (a cyclo‐oxygenase inhibitor) on spontaneous and evoked contractions of isolated lymphatic vessels was investigated. Aspirin at doses of 10−6m or greater depressed both spontaneous and action potential‐dependent evoked contractions, but failed to inhibit contractions evoked by high current field stimulation. These latter contractions were rapidly depressed by the application of D600. When aspirin was applied for five minute periods, inhibition never occurred within the period of drug administration but was delayed, with maximum inhibition occurring approximately 10 min after washout of the drug. It is concluded that the inhibitory action of aspirin is unlikely to be a non‐specific depression of the contractile mechanism, but rather a reduction in excitability probably as a result of cyclo‐oxygenase inhibition.

Endothelium‐dependent modulation of pacemaking in lymphatic vessels of the guinea‐pig mesentery.

“…Indomethacin caused a decrease in the contractile activity of perfused vessels. This is consistent with the finding that spontaneous activity in lymphatic vessels is modulated by arachidonic acid metabolites (Johnston & Gordon, 1981) and is suppressed by the cyclo-oxygenase inhibitors indomethacin and aspirin (Johnston & Feuer, 1983;Allen, Burke, Johnston & McHale, 1984). The results from the present study show that the endothelium-dependent modulation of constriction frequency induced by ACh stimulation is due to release of EDNO, which causes an increase in membrane conductance with associated hyperpolarization and a direct suppression of STDs in the lymphatic smooth muscle, mediated by EDNO.…”

Interaction of Inflammatory Mediators with the Lymphatic Vessel

“…1981;] Leukotriene B4 Leukotriene C4 Leukotriene D4 Arachidonic acid PGA2 [Ohhashi and Azuma, 1984] PGB2 [Ohhashi and Azuma. 1984] Bradykinin Azuma et al, 1983] Histamine [Ohhashi et al, 1978; Serotonin [Ohhashi et al, 1978; Mediators that suppress contractile activity in vitro PGE| and PGE2 Ohhashi and Azuma, 1984] Prostacyclin [Ohhashi and Azuma, 1984] Arachidonic acid Vasoactive intestinal peptide Substance P Neurotensin [Ohhashi ct al., 1983] Leucine-enkephaline Methionine-enkephaline [Ohhashi ct al., 1983] ited spontaneous and action-potential-dependent, electrically evoked contractions, it did not suppress contractions that were pro duced by high-current field stimulation, whereas D600 suppressed both types of ac tivity [Allen et al, 1984], This result demon strated that the inhibition of contractions by aspirin at least, was not via a nonspecific depression of the contractile mechanism.…”

“…Allen et al [1984] have postulated that arachidonate metabolites may provide a background excit ability that would facilitate the responses of the vessels to stretch, circulating mediators and nerve stimulation. However, the effects of arachidonate on the electrical activity of the lymphatics have not been assessed and the metabolites generated in the vessel wall have not been characterized.…”

Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity

“…A similar vasorelaxant effect of ACh via nitric oxide is well described in animal lymphatics, including canine thoracic duct (41), guinea pig mesenteric lymphatics (43), and rat iliac lymph node afferent vessels (22). Cyclooxygenase inhibition by indomethacin or aspirin application has been reported to suppress both spontaneous and evoked changes in lymphatic pumping in isolated animal lymphatics (2,10,14,17), and in vivo administration of indomethacin to volunteers with catheterized subcutaneous lymphatics does not alter measured end pressures or rhythmic pressure waves (37). L-NAME and indomethacin administration to the human thoracic duct, to inhibit NO and prostaglandin production, respectively, did not inhibit spontaneous activity, suggesting that these factors modulate pumping frequency but are not of importance for the generation of this activity.…”