AJP - Regulatory, Integrative and Comparative Physiology, Vol 265, Issue 4 772-R780, Copyright © 1993 by American Physiological Society
The effect of pregnancy on the response to the TxA2/PGH2 analogue U-46619 in rabbits
G. Losonczy, I. Mucha, J. DiPirro, J. Sweeney, G. Brown, J. Brentjens and R. Venuto
Department of Medicine, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14215.
We compared the hemodynamic actions of U-46619, a stable thromboxane A2
(TxA2) prostaglandin H2 (PGH2) analogue, in nonpregnant (NP) rabbits with
those observed in late pregnant (P) rabbits. An intravenous injection of
U-46619 (10 micrograms) to each of eight NP chronically instrumented
rabbits (mean body weight 3.4 kg) induced an immediate (1 min) and
reversible fall of cardiac output (CO, 66%) and mean arterial pressure
(MAP, 41%, both P < 0.01). P rabbits (n = 6, mean body weight 3.8 kg),
however, responded with an elevation of MAP (5%, P < 0.02) upon
intravenous injection of the drug (10 micrograms), while CO remained
unchanged. The fall of CO in NP rabbits was associated with the temporary
disappearance of a fraction of circulating platelets between the superior
vena cava and the aortic arch. The number of platelets at 30 and 60 s after
U-46619 was reduced (P < 0.05) by 14 and 20% respectively in the aortic
blood, whereas caval platelet counts were unchanged until 90 s (-6%, P <
0.05). In contrast, intraaortic administration of this drug (10 micrograms)
to NP rabbits resulted in neither thrombocytopenia nor hypotension. U-46619
(10-30 micrograms i.v.) caused no decrease in platelet count in the aorta
of P rabbits. In vitro, U-46619-induced aggregation of platelets harvested
from P rabbits was also blunted (P < 0.001). This could not be
attributed to reduced affinity or number of platelet thromboxane receptors.
The data indicate that U-46619 induces a fall of arterial pressure
simultaneous with intravascular platelet aggregation.(ABSTRACT TRUNCATED AT
250 WORDS)
