Lecture 11: Arachidonic Acid Pathway Flashcards
Eicosanoids are products of oxygenation of…
Polyunsaturated long-chain fatty acids, including arachidonic acid (most abundant eicosanoid precursor), released from membrane
Products of the COX pathway
Prostaglandins, prostacyclin, thromboxane
Effects of prostaglandins on vascular SM
Vasoconstrictors (TXA2 and PGF2alpha) AND vasodilators (PGI2 and PGE2)
PGI2
Vasodilation and inhibition of SM proliferation
TXA2
Vasoconstriction and SM mitogen
COX1 and COX2
COX1 = found in all tissues, especially in GI; COX2 = upregulated in kidney, GI, CNS, endothelium
Contraction of longitudinal, circular muscles in GI tract
PGF2 (also causes vasoconstriction)
Relaxation of circular muscles
PGE2 (also causes vasodilation)
Contraction of respiratory SM
TXA2, PGF2alpha
Relaxation of respiratory SM
PGE2, PGI2
Inhibit platelet aggregation
Higher concentration of PGE2, PGD2, PGI2
TXA2 and platelets
Directly enhances platelet aggregation and augments other platelet agonists (thrombin)
Vasodilation in kidney: mediators, where, and effect on GFR
Most in afferent arteriole, PGE2 and PGI2, increase GFR (GOOD)
PGE2 and PGI2 stimulates ________ release. Results in?
Renin –> increased AII –> constricted efferent arteriole –> increased hydrostatic pressure –> increase GFR (GOOD)
TXA2 and the kidney
Renal constriction (mostly afferent) –> decreased GFR
Net effect of eiconsanoids on GFR is to ___________ GFR
Increase (TXA2 not as strong)
PGE2 and PGI2 effect on Na+ and water
Increases Na+ excretion (via decreased Na+ resaobsorption) and increases water excretion (via attenuated ADH)
PGE2 and PGI2 effect on blood pressure via excretion
Maintains a low blood pressure
What is the net of effect of prostaglandins on BP? What are the two things behind this balance?
Decrease BP: PGE2 and PGI2 –> balance b/t Na+ and H2O excretion (decrease BP) VS increase in renin (increase BP)
What prostaglandins increase body temperature? Why does this make sense?
PGE2, PGF2alpha, PGI2; NSAIDs are FEVER REDUCERS
Effects of PGE on neurotransmission
PGE inhibit release of NE from sympa postganglionic nerve endings, leading to LESS VASOCONSTRICTION
Two reasons that COX inhibition causes vasoconstiriction
Leads to NE release AND inhibit synthesis of vasodilators (PGE2 and PGI2)
Peripheral nerve endings are sensitized to pain by…How?
PGE2 and PGI2; increased membrane excitability
Prostaglandins effects on CNS pain modulation (3)
Increase excitability of spinal dorsal horn neurons, augment pain intensity, widen pain perception area
Effects of PGE2 and PGI2 on inflammation
Increase vascular permeability and leukocyte infiltration
Prostaglandins in the eye…
PGE and PGF derivatives lower intra ocular pressure (Latanoprost)
LOX pathway creates what? What do these do (main, opposing actions)?
HETEs, leukotrienes, lipoxins; Leukotrienes: Potent chemoattractants for eos and T-cells –> inflammation; Lipoxins: activate macrophages, inhibit eos, lymphocytes
Leukotrienes are a product of the LOX pathway. Importance for airways?
Bronchoconstrictors –> bronchoconstriction, increased permeability, and increased mucus secretion
NSAIDs and airways
10% of patients taking NSAIDs have bronchospasm likely from shifting arachidonate metabolism from COX to the leukotriene arm
Cytochrome P450/EET and LOX pathways on the heart
LOX –> proliferation of SM In vascular, decreased coronary blood flow, decreased contractility; EET –> vasodilation of cardiac vessels
