Abstract
The aim of our study was to evaluate the effects of thromboxane A 2 (TXA 2) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA 2 receptor antagonist and synthase inhibitor (BM-573). Twelve anesthetized pigs were randomly assigned in two groups: in Ago group ( n = 6), the animals received six consecutive injections of U-46619 at 30 min interval, while in Anta group ( n = 6) they received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. The effects of each dose of BM-573 on ex vivo platelet aggregation induced by arachidonic acid, collagen or ADP were also evaluated. Vascular properties such as characteristic impedance, peripheral resistance, compliance, arterial elastance were estimated using a windkessel model. Intravenous injections of 0.500 mg/ml of BM-573 and higher doses resulted in a complete inhibition of platelet aggregation induced by arachidonic acid. In the same conditions, BM-573 completely blocked the increase of arterial elastance, and stabilized both mean aortic blood pressure and mean systemic blood flow. In conclusion, BM-573 could therefore be a promising therapeutic approach in pathophysiological states where TXA 2 plays a main role in the increase of vascular resistance like in pathologies such as systemic hypertension.
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