Vol. 88, Issue 4, 1167-1174, April 2000
Prostaglandins potentiate U-46619-induced pulmonary
microvascular dysfunction
Joseph K.
Wright1,
Lawrence T.
Kim1,
Thomas E.
Rogers2, and
Richard H.
Turnage1
Departments of 1 Surgery and
2 Pathology, University of Texas Southwestern
Medical School and Dallas Veterans Affairs Medical Center, Dallas,
Texas 75216
The induction of cyclooxygenase is an
important event in the pathophysiology of acute lung injury. The
purpose of this study was to examine the synergistic effects of various
cyclooxygenase products (PGE2, PGI2,
PGF2
) on thromboxane A2
(TxA2)-mediated pulmonary microvascular dysfunction. The
lungs of Sprague-Dawley rats were perfused ex vivo with Krebs-Henseleit
buffer containing indomethacin and PGE2 (5 × 10
8 to 1 × 107 M), PGF2 (7 × 109 to 5 × 106 M), or PGI2 (5 × 108 to 2 × 105 M). The TxA2-receptor
agonist U-46619 (7 × 108 M) was
then added to the perfusate, and then the capillary filtration coefficient (Kf), pulmonary arterial pressure
(Ppa), and total pulmonary vascular resistance (RT) were
determined. The Kf of lungs perfused
with U-46619 was twice that of lungs perfused with buffer alone
(P = 0.05). The presence of PGE2,
PGF2, and PGI2 within the perfusate of lungs
exposed to U-46619 caused 118, 65, and 68% increases in
Kf, respectively, over that of lungs perfused with
U-46619 alone (P < 0.03). The RT of lungs
perfused with PGE2 + U-46619 was ~30% greater than that
of lungs exposed to either U-46619 (P < 0.02) or
PGE2 (P < 0.01) alone. When paired measurements
of RT taken before and then 15 min after the addition of
U-46619 were compared, PGI2 was found to attenuate
U-46619-induced increases in RT (P < 0.01). These
data suggest that PGE2, PGI2, and
PGF2 potentiate the effects of TxA2-receptor
activation on pulmonary microvascular permeability.
capillary filtration coefficient; pulmonary vascular resistance; isolated perfused lung model
