SUMMARY Leukotriene D 4 , a constituent of slow-reacting substance of anaphylaxis, elicits a pressor response followed by nypotensive 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 radiolabeleti microspheres. One minute after leukotriene D 4 administration (20 fig/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 D 4 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 D 4 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 D 4 -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. (Hypertension 7: 507-513, 1985) KEY WORDS • leukotrienes • blood pressure • cardiac output • total peripheral resistance • regional blood flow • regional vascular resistance • spontaneously hypertensive rats • Wistar-Kyoto rats A CUTE anaphylaxis is characterized by severe / \ hemodynamic changes, cardiac arrhythmias, A. \ -and myocardial ischemia. All these phenomena can be elicited by systemic or intracardiac administration of slow-reacting substance of anaphylaxis. 1 " 3 Recently, leukotriene D 4 (LTD 4 ) and C 4 (LTC 4 ), 5-lipoxygenase metabolites of arachidonic acid, were identified as major constituents of slow-reacting substance of anaphylaxis^ and were shown to cause bronchoconstriction, 4. 7. 8 vasoconstnction, 4. 7-14 cardiodepression, 9 l2~16 and increased venular permeabil- j t y 4.6. i7. i8 Aft er systemic administration of leukotrienes to some animal species, an initial arteriolar constriction and rise in blood pressure are followed by a transient hypotensive period. This biphasic response to LTD,, and LTC 4 is characteristic of guinea pig, monkey, and sheep 7 ' l2 -l4 but is uncommon in various species of rats."-' 3 -l9~21 Spontaneously hypertensive rats (SHR), however, are extremely sensitive to the cardiovascular effects ...