Low-dose thromboxane A2 receptor stimulation promotes closure of the rat ductus arteriosus with minimal adverse effects

Background: Patent ductus arteriosus (PD a ) is a common life-threatening complication among premature infants. a lthough cyclooxygenase inhibitors are frequently used to treat PD a , as they inhibit the synthesis of prostaglandin e 2 , the most potent vasodilator in the ductus arteriosus (D a ), their efficacy is often limited. a s thromboxane a 2 (TX a 2 ) induces vascular contraction via the TX a 2 receptor (TP), we hypothesized that TP stimulation would promote D a closure. Method: To measure the inner diameter of the vessels, a rapid whole-body freezing method was used. r esults: Injection of the selective TP agonists U46619 and I-BOP constricted the fetal D a at embryonic day 19 (e19) and e21 in a dose-dependent manner. Of note, U46619 also exerted a vasoconstrictive effect on two different types of postnatal PD a models: premature PD a and hypoxia-induced PD a . We also found that U46619 constricted the ex vivo D a ring to a greater extent than it constricted the ex vivo aorta. Furthermore, we found that U46619 at lower concentrations (up to 0.05 mg/g of body weight) had a minimal vasoconstrictive effect on other vessels and did not induce microthrombo sis in the pulmonary capillary arteries. c onclusion: Low-dose TP stimulation constricts the D a