Role of Prostacyclin in the Cardiovascular Response to Thromboxane A 2

Abstract

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 .