Figure 20-18 Synthesis of renal prostaglandins. Phospholipase A₂ is stimulated by ischemia, norepinephrine, and angiotensin II and cleaves arachidonic acid from its bond with membrane phospholipid. Cyclooxygenase acts on arachidonic acid to form evanescent cyclic endoperoxides (PGG₂ and PGH₂ ). The action of isomerase and prostacyclin synthetase culminates in formation of the vasodilator prostaglandins PGD₂ , PGE₂ , and PGI₂ (prostacyclin), which oppose the action of the renin-angiotensin system on the kidney and protect against ischemic stress. Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs predisposes the kidney to damage. Under hypoxic or ischemic conditions, cyclic endoperoxides undergo reduction to the vasoconstrictor PGF₂ , which acts on thromboxane receptors. Endotoxin increases the activity of leukocyte lipoxygenase and thromboxane synthetase. Leukotrienes (especially C₄ and D₄ ) and thromboxane (TXA₂ ) induce renal vasoconstriction and contribute to the vasomotor nephropathy of sepsis.