Figure 157

Renal injury from exposure to cyclosporin A. Cyclosporin A is one example of a toxicant that acts at several sites within the kidney. It can injure both endothelial and tubular cells. Endothelial injury results in increased vascular permeability and hypovolemia, which activates the sympathetic nervous system. Injury to the endotheli-um also results in increases in endothelin and thromboxane A2 and decreases in nitric oxide and vasodilatory prostaglandins. Finally, cyclosporin A may increase the sensitivity of the vascula-ture to vasoconstrictors, activate the renin-angiotensin system, and increase angiotensin II levels. All of these changes lead to vasoconstriction and hypertension. Vasoconstriction in the kidney contributes to the decrease in glomerular filtration rate (GFR), and the histologic changes in the kidney are the result of local ischemia and hypertension.

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