Evidence for high and low affinity leukotriene D4 receptors mediating vascular responses in the conscious rat.

Leukotriene D4 (0.17-17 nmol/kg i.v.) produced a dose-dependent increase in blood pressure in the conscious rat. Infusion of the selective peptidoleukotriene receptor antagonist, SK&F 104353, produced dose-dependent shifts in the leukotriene D4 dose-response curve. However, SK&F 104353 at doses of 0.2 mg/kg + 1 mg/kg per h or 1 mg/kg + 3 mg/kg per h produced similar dose ratios of 9.2 +/- 1.1 and 9.2 +/- 1.6, respectively. The peptidoleukotriene receptor antagonist, ICI 198615, also shifted the LTD4 dose-response curve, although doses of 0.2 mg/kg + 1 mg/kg per h, 1 mg/kg + 3 mg/kg per h or 2 mg/kg + 10 mg/kg per h produced similar dose ratios of 15.7 +/- 3.4, 19.1 +/- 6.3 and 16.2 +/- 3.6, respectively. The similarity in the dose ratios observed despite increasing doses of either SK&F 104353 or ICI 198615 suggests the existence of two vascular leukotriene D4 receptor subpopulations, differentiated by high and low agonist affinity.