Prostanoids are synthesized from arachidonic acid by either COX-1 or COX-2, and play an important role in maintaining homeostasis in many body tissues. The expression of COX-1 in most tissues is relatively constant (constitutive), while COX-2 expression is typically minimal, but becomes selectively upregulated under inflammatory conditions. Exceptions to this general rule include endothelial cells lining the arterioles in the cardiovascular system & kidney, where COX-2 expression is significant even in the absence of inflammation.
1) Stomach
In the stomach, COX-1 mediated production of prostaglandins PGE2 & PGI2 plays an important role in regulating the production of bicarbonate and mucus, as well as regulating normal blood flow. Each of these effects helps to protect the cells lining the wall of the stomach from the erosive effects of stomach acid (stomach fluid has a normal pH of 1.5-3.5).
Hence, blocking COX-1 mediated production of prostaglandins in the stomach by aspirin and other non-selective NSAIDs (e.g. ibuprofen, naproxen) is expected to increase the incidence of peptic ulcers (and associated symptoms including bleeding & pain).
2) Kidney
Renal prostaglandins function primarily as vasodilators in the kidneys. In healthy individuals, the impact of prostaglandins on renal perfusion is relatively limited. However, in the setting of prolonged renal vasoconstriction that develops during settings of advanced age, heart failure, and kidney failure, prostaglandin synthesis is upregulated. Under these conditions when kidney function is compromised, the production of prostaglandins serves an important role to preserve renal blood flow and protect the glomerular filtration rate (GFR) by decreasing pre-glomerular (afferent) arterial resistance . In this setting, even episodic use of NSAIDs can decrease blood flow through the glomerulus, and increase the risk of acute kidney injury.
Thanks for watching and don't forget to SUBSCRIBE,
hit the like button👍🏻and click the bell button🔔 for future notifications!!!
