The effect of pregnancy on the response to the TxA2/PGH2 analogue U-46619 in rabbits.
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)
Losonczy
G
G
Department of Medicine, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14215.
Mucha
I
I
DiPirro
J
J
Sweeney
J
J
Brown
G
G
Brentjens
J
J
Venuto
R
R
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000378:metabolism*; D012016:Reference Values
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; C061750:7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid