AJP - Regulatory, Integrative and Comparative Physiology, Vol 268, Issue 2 366-R374, Copyright © 1995 by American Physiological Society
TxA2 receptor activation elicits organ-specific increases in microvascular permeability in the rat
F. Bertolino, J. P. Valentin, M. Maffre, A. M. Bessac and G. W. John
Division of Cardiovascular Diseases II, Centre de Recherche Pierre Fabre, Castres, France.
We investigated whether the stable thromboxane A2 (TxA2) analogue U-46619
had any direct effect on extracellular fluid partition. In anesthetized
open-chest rats, U-46619 (1.25 and 20 micrograms/kg iv) dose dependently
increased mean pulmonary arterial pressure and hematocrit, whereas mean
systemic arterial pressure was raised only at the low dose of agonist. The
increase in hematocrit (13.2 +/- 2.9% at 20 micrograms/kg; P < 0.05)
still occurred in bilaterally nephrectomized rats and in binephrectomized
plus splenectomized rats (11.6 +/- 2.7 and 12.2 +/- 4.6%, respectively;
both P = NS vs. U-46619 in control rats), corresponding to a calculated
decrease in plasma volume of 22.1 +/- 4.5, 19.6 +/- 4.0, and 19.2 +/- 5.8%,
respectively. Plasma protein concentration increased less than hematocrit,
and the coefficient of reflection was significantly lower in these groups,
suggesting protein extravasation. Additional experiments showed that
U-46619 (1.25 and 10 micrograms/kg iv) dose dependently increased the
vascular leak of albumin mainly in lung, kidneys, and spleen but not in
brain, liver, mesentery, and cardiac and skeletal muscles. Pretreatment
with the TxA2 receptor antagonist SQ-29,548 (2.5 mg/kg iv bolus plus 2.5
mg.kg-1.h-1 as maintenance) abolished all effects of U-46619, including the
increase in mean pulmonary arterial pressure, hematocrit, plasma protein
concentration, and albumin extravasation and the decrease in mean systemic
arterial pressure, plasma volume, and coefficient of reflection.(ABSTRACT
TRUNCATED AT 250 WORDS)
