Arachidonic Acid Metabolites (Prostaglandins and Related Compounds)
Prostaglandins and related compounds (collectively referred to as prostanoids or eicosanoids) such as prostacyclin (PGI2), leukotrienes (LTs) and thromboxanes (TXs) are produced by many different cells in the body. Although their primary physiological actions are generally related to inflammation and hemostasis, by nature they all are vasoactive and can modulate cardiovascular function, particularly vascular tone. Their effects are very localized because they are paracrine hormones; that is, they are released by one cell and act on nearby cells.
There are different forms of the COX enzyme, two of which are COX-1 and COX-2. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and acetaminophen (Tylenol®) are non-selective inhibitors of the COX enzymes. Newer NSAIDs are relatively selective for COX-2, and generally have fewer gastrointestinal-related side effects. COX-1 is constitutive and therefore produces prostanoids under basal conditions. In contrast, COX-2 is inducible and is upregulated during inflammation.
Smooth muscle cells in blood vessels produce prostaglandins (PGs). PGE2 generally acts as a vasodilator by stimulating the Gs-protein pathway, whereas PGF2α commonly produces vasoconstriction by stimulating the Gq-protein pathway.
Vascular endothelium produces PGI2 as its primary derivative of arachidonic acid. This prostanoid is a potent vasodilator and inhibitor of platelet adhesion to the endothelium, and acts through the Gs-protein pathway. Therefore, it is anti-thrombotic. These actions are similar to those of endothelium-derived nitric oxide. Endothelial dysfunction or damage, which occurs in atherosclerosis, for example, can cause vasospasm and thrombosis.
Platelets produce TXA2, which is a potent vasoconstrictor acting through the Gq-protein pathway. Its production is enhanced during inflammation and tissue injury, and following platelet activation. It is important in producing arterial vasoconstriction when a vessel is cut and bleeding (hemostatic function).
Leukocytes produce leukotrienes such as LTC4 in response to inflammation and tissue injury. Like TXA2, it is a potent vasoconstrictor and acts through the Gq-protein pathway. Leukotrienes (and prostaglandins) can also make the vascular endothelium more "leaky" thereby promoting edema formation during inflammation.
RK Revised 04/06/2007