Differential hemodynamic effects of leukotriene D4 in anesthetized rats: evaluation by directional pulsed Doppler...

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.