Hypertension, Vol 7, 507-513, Copyright © 1985 by American Heart Association
Z Zukowska-Grojec, MA Bayorh, IJ Kopin and G Feuerstein
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.
ARTICLES
Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats
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