We investigated the comparative direct and cyclooxygenase-mediated effects of the constituents of slow-reacting substance of anaphylaxis (SRS-A), i.e., leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4) on pulmonary and systemic haemodynamics of sheep. In 20 conscious sheep, measurements of pulmonary vascular resistance (Rpv) and systemic vascular resistance (Rsv) were obtained before and after a rapid intravenous injection of LTC4 (0.1 μg.kg-1), LTD4 (0.1 μg.kg-1) and LTE4 (1 μg.kg-1). The same protocol was carried out after pretreatment with the leukotriene antagonist FPL-57231 or the cyclooxygenase inhibitor indomethacin. LTD4 increased mean Rpv to 421% of baseline (p<0.001) and had a biphasic effect on mean Rsv, which, following an initial decrease of 18% (p<0.05), increased to 143% of baseline (p<0.05). LTC4 and LTE4 had no significant efffects on Rpv, while they increased mean Rsv to 144% and 143% of baseline, respectively (p<0.05). This effect was not prreceded by a decrease in Rsv. FPL-57231 completely blocked the effects of LTC4, LTD4 and LTE4 on Rsv, and of LTD4 on Rpv. Indomethacin had no effect on LTC4, LTD4 and LTE4-induced initial increases in mean Rsv, while it prevented the LTD4-induced initial decrease in mean Rsv. Indomethacin also prevented the LTD4-induced increase in Rpv. A dose-response curve (0.05, 0.1, 0.5 and 1 μg.kg-1) demonstrated that in raising Rsv, LTE4 was approximately 10 times less potent than LTC4 and LTD4. We conclude that: a) LTC4, LTD4 and LTE4 have differential effects on pulmonary and systemic circulations of sheep, b) the effects of LTC4 and LTE4 are mediated directly by vascular leukotriene receptor stimulation, and c) LTD4 has both direct and indirect (cyclooxygenase mediated) vascular effects.
|Original language||English (US)|
|Number of pages||8|
|Journal||Clinical Respiratory Physiology|
|State||Published - Dec 1 1986|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine