Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal ischemia and reperfusion (I/R) injury is the major cause of acute renal failure and may also be involved in the development and progression of some forms of chronic kidney disease. We previously showed that a mineralocorticoid receptor (MR) blockade prevents renal vasoconstriction induced by cyclosporine that leads to acute and chronic renal failure (Feria I, Pichardo I, Juarez P, Ramirez V, Gonzalez MA, Uribe N, Garcia-Torres R, Lopez-Casillas F, Gamba G, Bobadilla NA. Kidney Int 63: 43-52, 2003; Perez-Rojas JM, Derive S, Blanco JA, Cruz C, Martinez de la Maza L, Gamba G, Bobadilla NA. Am J Physiol Renal Physiol 289: F1020-F1030, 2005). Thus we investigated whether spironolactone administration prevents the functional and structural damage induced by renal ischemia-reperfusion (I/R). Five groups were studied: sham-operated animals, rats that underwent 20 min of ischemia and 24 h of reperfusion, and three groups that received spironolactone 1, 2, or 3 days before I/R, respectively. Renal I/R produced significant renal dysfunction and tubular damage. Spironolactone administration completely prevented a decrease in renal blood flow, the development of acute renal failure, and tubular apoptosis. The protection conferred by spironolactone was characterized by decreasing oxidative stress, as evidenced by a reduction in kidney lipoperoxidation, increasing expression of antioxidant enzymes, and restoration of urinary NO(2)/NO(3) excretion. Endothelial nitric oxide synthase expression was upregulated by a mineralocorticoid receptor blockade in I/R groups; in addition, an increase in activating phosphorylation of this enzyme at residue S1177 and a decrease in inactivating phosphorylation at T497 were observed. In conclusion, our study shows that spironolactone administration prevents the renal injury induced by I/R, suggesting that aldosterone plays a central role in this model of renal injury.
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PMID:Renal ischemia-reperfusion injury is prevented by the mineralocorticoid receptor blocker spironolactone. 1737 67

Acute kidney injury induced by renal ischemia-reperfusion (I/R) compromises microvascular density and predisposes to chronic kidney disease (CKD) and sodium-dependent hypertension. VEGF-121 was administered to rats fed a standard (0.4%) sodium diet at various times following recovery from I/R injury for up to 35 days. VEGF-121 had no effect on the initial loss of renal function, as indicated by serum creatinine levels measured 24 h after injury. Serum creatinine levels declined thereafter, indicative of renal repair. Rats were then switched to an elevated (4.0%) sodium diet for an additional 28 days to induce CKD. The 4.0% sodium diet enhanced renal hypertrophy, interstitial volume, albuminuria, and cardiac hypertrophy relative to postischemic animals maintained on the 0.4% sodium diet. Administration of VEGF-121 from day 0 to 14, day 0 to 35, or day 3 to 35 after I/R suppressed the effects of sodium diet on CKD development, while delayed administration of VEGF-121 from day 21 to 35 had no effect. Endothelial nitric oxide synthase protein levels were upregulated in postischemic animals, and this effect was significantly increased by the 4.0% sodium diet but was not influenced by prior treatment with VEGF. Conversely, microvascular density was preserved in postischemic animals treated with VEGF-121 relative to vehicle-treated postischemic animals. These data suggest that early, but not delayed, treatment with VEGF-121 can preserve vascular structure after ischemia and influence chronic renal function in response to elevated sodium intake.
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PMID:VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury. 1879 50