Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats

Leukotriene D4, a constituent of slow-reacting substance of anaphylaxis, elicits a pressor response followed by hypotensive shock in spontaneously hypertensive rats but not in other rats. Hemodynamic mechanisms underlying this pattern in spontaneously hypertensive rats, pithed and vagotomized to eliminate circulatory reflexes, were studied using radiolabeled microspheres. One minute after leukotriene D4 administration (20 micrograms/kg i.v.), mean arterial pressure increased by 54 mm Hg, total peripheral resistance index increased by 68%, heart rate decreased by 34 beats/minute, and cardiac index was unchanged. Profound reductions of blood flow and increases of vascular resistance in the hepatosplanchnic area, skeletal muscles, and skin also occurred. Five minutes later, mean arterial pressure remained elevated (+35%), hematocrit rose (+17%), and total peripheral resistance index increased, which offset 40% decreases in cardiac and stroke volume indices. Ten minutes after leukotriene D4 administration, during hypotension, cardiac and stroke volume indices and blood flow to all vascular beds declined further while total peripheral resistance index and hematocrit (+28%) continued to rise. In Wistar-Kyoto rats, administration of leukotriene D4 caused less of a pressor response (+34 mm Hg) because vascular resistance was increased only in skeletal muscles, which was followed by a slight hypotension without any significant changes in cardiac and stroke volume indices, total or regional vascular resistance, and hematocrit. Thus, in spontaneously hypertensive rats the leukotriene D4-induced pressor response appears to be caused by generalized vasoconstriction, and the subsequent hypotension appears to result not from vascular collapse but from reduced cardiac output.