Effects of STA(2), a thromboxane A(2) mimetic, in inducing airflow obstruction and airway microvascular leakage in guinea pigs.
BACKGROUND
U-46619, a thromboxane A(2) (TXA(2)) mimetic, is shown to cause airway microvascular leakage, although the effects is weak when comparing with that to induce bronchoconstriction in guinea pigs.


OBJECTIVE
In order to know the airway effect of TXA(2) more accurately, we have examined the effects of STA(2), a TXA(2) mimetic with higher affinity to TXA(2) (TP) receptors than U-46619, to induce airway microvascular leakage and airflow obstruction.


METHODS
Anesthetized and ventilated guinea pigs were i.v. given STA(2) (3-30 nmol/kg) or U-46619 (3-100 nmol/kg) 1 min after i.v. Evans blue dye. STA(2)- and U-46619-induced increases in lung resistance (R(L)) was measured for 6 min. The amount of extravasated Evans blue dye in the lower airways was, then, examined as an index of leakage. In selected animals, specific TP receptor antagonists (10 microg/kg S-1452 or 10 mg/kg ONO-3708) were pretreated i.v.


RESULTS
Both STA(2) and U-46619 induced significant increases in leakage and airflow obstruction. However, STA(2) induced a slow and significantly less increase in R(L) but caused a significantly greater increase in extravasation of Evans blue dye compared to U-46619. Specific TP receptor antagonists completely abolished both airway effects induced by STA(2) and U-46619.


CONCLUSIONS
Our present results have supported a possibility that TXA(2) induces microvascular leakage as well as bronchoconstriction in the airways.
Inoue
Yoshinari
Y
Department of Pediatrics, Gunma University School of Medicine, Maebashi, Japan.
Tokuyama
Kenichi
K
Nishimura
Hideko
H
Arakawa
Hirokazu
H
Kato
Masahiko
M
Mochizuki
Hiroyuki
H
Morikawa
Akihiro
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000402:Airway Obstruction / Q000139:chemically induced / Q000503:physiopathology*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000209:etiology / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006168:Guinea Pigs; D008168:Lung / Q000098:blood supply*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; D014662:Vasoconstrictor Agents; C056566:S 145; D005070:Evans Blue; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C037866:STA 2; C049855:ONO 3708