Vascular responses to leukotriene B4, C4 and D4 following FPL 55712, indomethacin, saralasin, phentolamine and verapamil in the conscious rat

1 The pressor and vascular permeability effects of leukotrienes B4 (LTB4), C4 and D4 were investigated in conscious unrestrained rats. 2 Leukotrienes C4 and D4 (3.2–51 nmol kg−1 i.v.) caused an acute dose‐dependent elevation of the mean arterial pressure, which was maximal after 2 min and returned to control levels within 14 min. Heart rate was significantly reduced by the higher doses of LTC4 and LTD4. LTB4 (up to a dose of 51 nmol kg−1) was essentially inactive. 3 These effects of LTC4 and LTD4 were abolished by FPL 55712, a putative antagonist of sulphidopeptide leukotrienes and by verapamil, a calcium channel blocker. 4 Indomethacin, phentolamine or saralasin pretreatment failed to modify the pressor response to LTC4 and LTD4. 5 LTC4 and LTD4 furthermore caused an increase in haematocrit values, which was significantly attenuated by FPL 55712, indomethacin and verapamil. 6 The present findings show that the pressor effect of LTC4 and LTD4 is not related to prostanoid release and can be reversed by calcium channel blockade; whereas the effect on vascular permeability seems to require the presence of both cyclo‐oxygenase product(s) and calcium.