Effects of a cGMP-specific phosphodiesterase inhibitor on expression of endothelial @entity842 synthase and @entity6667 in @entity35 with XXXX -induced nephrotoxicity.

@entity8 @entity82 @entity28281 @entity870 @entity63 @entity1711 @entity205 @entity1710 @entity842 @entity1011 @entity35 @entity6667
BACKGROUND: The mechanism of @entity205 ( @entity870 )-induced nephrotoxicity has been suggested to be vasoconstriction due to reduced @entity842 (NO), providing tissue @entity82 by elevation of transforming growth factor beta and @entity6667 ( @entity6667 ). In this study using a @entity35 model of CsA-induced nephrotoxicity, we administered a phosphodiesterase-5 inhibitor to ameliorate the @entity8 and alter the expression of endothelial No synthase (eNOS) and @entity6667 . METHODS: A right nephrectomy was performed in @entity35 (n = 30; 200-250 g, all male). The @entity63 group (n = 6) underwent ligation of the @entity8 for 45 minutes (IR) before observation for 28 days. After IR, the @entity28281 group (n = 6) was treated with 10 mg/kg drug orally, the CsA group (n = 6) received 15 mg/kg CsA injected subcutaneously and the CsA plus @entity28281 group (n = 6) received 15 mg/kg CsA injected subcutaneously together with the oral administration of 10 mg/kg @entity28281 . RESULTS: Administration of @entity28281 significantly decreased serum @entity1011 either alone (0.21    0.04 mg/dL) or in combination with CsA (1.86    0.35 mg/dL) versus the @entity63 (0.85    0.22 mg/dL) and the CsA alone (3. 10    0.77 mg/dL) group. (P = .002; P = .002). Comparing the @entity1710 - @entity1711 staining of the @entity63 (0.41    0.09) and CsA (0.44    0.08) groups showed a significantly decreased loss of nuclei in proximal tubules after the administration of @entity28281 (0.27    0.05 [P = .004] and 0.26    0.02 [P = .002] respectively). Immunohistochemical staining showed strong eNOS staining in the @entity28281 and CsA plus @entity28281 groups. Western blots for eNOS showed decreased expression in the CsA group and increased expression in the @entity28281 group. Western blots for @entity6667 revealed reduced expression only in the CsA plus @entity28281 group. eNOS mRNA was decreased in the CsA (0.017    0.010) compared with the @entity63 group (0.048    0.015; P = .000). @entity6667 mRNA which was decreased in the CsA group (2.026    1.109), showed greater tendency after administration of @entity28281 (0.440    0.449) (P = .003). CONCLUSION: The phosphodiesterase inhibitor ameliorated @entity8 in a @entity35 model of CsA-induced nephrotoxicity, possibly related to increased eNOS and reduced @entity6667 expression.
