AJP - Heart and Circulatory Physiology, Vol 249, Issue 5 968-H973, Copyright © 1985 by American Physiological Society
Pulmonary and systemic vascular effects of SRS-A blockade in conscious lambs
T. J. Kulik, R. K. Schutjer, D. F. Howland and J. E. Lock
There is preliminary evidence suggesting that hypoxic pulmonary
vasoconstriction may be mediated by slow-reacting substance of anaphylaxis
(SRS-A), which is comprised of leukotrienes C4, D4, and E4. We studied the
effects of the SRS-A antagonist FPL 57231 (FPL) on the hypoxic pulmonary
vasoconstrictor response and on systemic vascular resistance in awake,
chronically instrumented young lambs. Two other studies were performed to
ascertain whether FPL's vasodilation was specific for hypoxic pulmonary
vasoconstriction: the effect of FPL infusion in pulmonary and systemic
vascular resistance was measured in six normoxic lambs, and the effect of
FPL on 5-hydroxytryptamine (5-HT)-mediated vasoconstriction was determined.
In seven lambs, mean pulmonary arterial pressure was 21 mmHg in room air
and 28 mmHg in hypoxia (Po2 = 43 Torr). During hypoxia, FPL infusion (2 mg
X kg-1 X min-1) reversibly decreased pulmonary arterial pressure to 15
mmHg; pulmonary arteriolar resistance also fell below normoxia levels with
FPL. FPL also caused a fall in aortic pressure and systemic vascular
resistance in these hypoxic lambs, but the decrease in systemic resistance
was less than the fall in pulmonary resistance. beta-Adrenergic blockade
using propranolol (1 mg/kg) did not affect the pulmonary vasodilation
caused by FPL. In six normoxic lambs, FPL infusion also significantly
decreased pulmonary and systemic vascular resistance (29% in each case).
These data are consistent with the idea that leukotrienes may be involved
in adjusting both pulmonary and systemic vascular tone, but further work is
necessary to establish whether FPL's vasodilation is mediated via its
leukotriene antagonism or is a nonspecific effect of FPL.
