Regulation of lymphatic contractility by arachidonate metabolites

Abstract

The circulation of lymph is apparently controlled partly by the pressure of fluid entering the lymphatic capillaries, aided by external forces such as skeletal muscle contraction and gut peristalsis^1,2, but lymphatic vessels themselves also contract rhythmically when distended in vivo or in vitro and this may be of major importance in the propulsion of lymph^3–8. We have studied the effects of biochemical mediators on isolated sheep and bovine lymphatic segments and on pressure pulses from indwelling lymphatic cannulae and report here that nanomolar concentrations of prostaglandin (PG) H₂ endoperoxide and a stable PGH₂ analogue elicited rhythmical contractions and increased the tone of isolated quiescent lymphatic segments. Some segments showed spontaneous rhythmic activity, and these spontaneous contractions could be inhibited not only by aspirin (a cyclo-oxygenase inhibitor) but also by inhibitors of thromboxane synthase (imidazole and compound UK 37248). The pulsatile pressure changes measured from indwelling lymphatic cannulae in conscious sheep were also suppressed by aspirin or imidazole infused directly into the lymphatic circulation. Our results suggest that endogenous thromboxane production is mainly responsible for spontaneous lymphatic contractions but that PGH₂ also has contractile activity. An unknown product of arachidonate and PGH₂, which could be formed non-enzymatically, inhibited both spontaneous and induced contractions.