Role of prostacyclin in the cardiovascular response to thromboxane A2

Thromboxane (Tx) A(2) is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA(2) formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI(2)) is a vasodilator that inhibits platelet function. Here we show that injury-induced vascular proliferation and platelet activation are enhanced in mice that are genetically deficient in the PGI(2) receptor (IP) but are depressed in mice genetically deficient in the TxA(2) receptor (TP) or treated with a TP antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors. Thus, PGI(2) modulates platelet-vascular interactions in vivo and specifically limits the response to TxA(2). This interplay may help explain the adverse cardiovascular effects associated with selective COX-2 inhibitors, which, unlike aspirin and nonsteroidal anti-Inflammatory drugs (NSAIDs), inhibit PGI(2) but not TxA(2).