Directed vascular expression of the thromboxane A(2) receptor results in intrauterine growth retardation

Thromboxane (Tx) A, is a platelet agonist, smooth muscle cell constrictor, and mitogen(1). Urinary Tx metabolite (Tx-M) excretion is increased in synd romes of platelet activation and early in both normal pregnancies and in pr egnancy-induced hypertension(2,3). A further increment occurs in patients p resenting with severe preeclampsia, in whom Tx-M correlates with other indi ces of disease severity(4). TxA(2) exerts its effects through a membrane re ceptor (TP), of which two isoforms (alpha and beta; refs. 5,6) have been cl oned. Overexpression of TP in the vasculature under the control of the pre- proendothelin-1 promoter(7) results in a murine model of intrauterine growt h retardation (IUGR), which is rescued by timed suppression of Tx synthesis with indomethacin. IUGR is commonly associated with maternal diabetes or c igarette smoking, both conditions associated with increased TxA(2) biosynth esis(8,9).