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Effect of prostanoids and thromboxanes on cardiovascular function. Arachidonic acid (AA) can be metabolized by cyclooxygenases (COX1/2) that reside within the nuclear membrane, endoplasmic reticulum, mitochondria, and the Golgi apparatus. AA is converted to the prostaglandin precursor PGG₂/H₂ that gives rise to a wide variety of prostanoids. Each prostanoid acts in an autocrine or paracrine manner through different receptors within the vascular endothelium, myocardium, and immune cells to regulate cardiovascular function. AA, arachidonic acid; COX, cyclooxygenase; DP, receptor for prostanoid D; EP, receptor for prostanoid E; FP, receptor for prostanoid F; IP, receptor for prostanoid I; PGG₂/H₂, prostaglandin G₂/H₂; PGI2, prostacyclin; PGD₂, prostaglandin D₂; PGE₂, prostaglandin E₂; PGF₂, prostaglandin F₂; TP, receptor for prostanoid TxA2; TxA2, thromboxane A2

Simplified schematic illustration of PG syntheses and their action on their high-affinity specific receptors. AAs are generated from membrane phospholipids, and then COX acts on AA to generate intermediate PG endoperoxide H (PGH₂). The tissue-specific PG synthase then converts PGH₂ into respective prostanoids. Use of NSAIDs or COX inhibitors can prevent the generation of prostanoids. Similarly, PG synthase inhibitors can prevent the generation of specific PG, whereas the use of selective receptor ligands can manipulate the outcome related to that specific receptor. According to the generalized hypothesis, those receptors that activate the cAMP pathway tilt the scale toward better outcomes after ischemic stroke, whereas those receptors that activate the Ca²⁺ pathway tilt the scale toward worse outcomes. However, this general rule is not always true, as has been shown recently. Abbreviations: cPGES-1, cytosolic PG E synthase-1; mPGES-1 and -2, membrane-associated PG E synthase-1 and -2; H-PGDS, hematopoietic PG D₂ synthase; L-PGDS, lipocalin-type PG D₂ synthase; PGFS, PG F_2α synthase; PGIS, PG I₂ (or prostacyclin) synthase; TxS, thromboxane synthase.