Leukotriene D4 (
LTD4) is the major constituent of
slow-reacting substance of anaphylaxis (
SRS-A). Cardiovascular depression and hypotensive
shock represent the major manifestations that attend systemic
anaphylaxis. To further evaluate the hemodynamic effects of
LTD4, we measured blood pressure (BP), heart rate (HR) and blood flow (BF) (directional pulsed Doppler
flowmeter) to different vascular beds (hindquarter, mesenteric and renal) of the
urethane-anesthetized rat.
LTD4 (3, 10 and 30 micrograms/kg, i.v.) caused a dose-dependent increase in BP: 15 +/- 3, 20 +/- 4 and 24 +/- 2 mm Hg, respectively, which was maximum after 2 min and returned to control level
at 10 min; HR was not significantly altered. BF to different vascular beds was differentially altered: mesenteric (-59%) greater than hindquarter (-38%) greater than renal (-10%). Vascular resistance (VR) increased by 195, 85 and 40% in mesenteric, hindquarter and renal beds, respectively.
Thyrotropin-releasing hormone (TRH) (2-5 mg/kg, i.v.) injected after
LTD4 increased BP, reversed the decrease in BF and the increase in VR in the mesenteric and hindquarter vascular beds. These data suggest that
LTD4 receptors are unevenly distributed in various vascular beds and that the splanchnic area is particularly vulnerable to
anaphylaxis-induced
ischemia. Furthermore,
Thyrotropin Releasing Hormone (TRH) might be useful to antagonize the hemodynamic consequences mediated by
SRS-A or
leukotriene.