Intrarenal administration of molsidomine, a molecule releasing nitric oxide, reduces renal ischemia-reperfusion injury in rats.
Ischemia reperfusion (I-R)-induced renal damage is reduced by systemic administration of the NO-dependent vasodilator molsidomine. The aim of this study was to estimate the effect of direct intrarenal molsidomine administration on renal dysfunction and inflammatory reaction after experimental I-R in rats, in order to assess only renal NO effects and to obviate its systemic hemodynamic action. Ischemia was induced by renal pedicle ligation (60 min) followed by reperfusion and contralateral nephrectomy. Molsidomine (4 mg/kg) was infused into the renal artery 15 min before reperfusion and its effects were compared with those of the NO-independent vasodilator hydralazine (2 mg/kg). Survival rates after 7 days were 100% in the sham-operated group and 75% in the I-R rats. Molsidomine treatment almost completely prevented the I-R-induced renal dysfunction, and survival reached 100%. Molsidomine prevented an I-R-induced increase in superoxide anion and reduced plasma levels of pro-inflammatory cytokines (TNF-alpha, IL-1beta and IFN-gamma), whereas it enhanced anti-inflammatory cytokines (IL-6 and IL-10). Inflammatory cell infiltration and cell-adhesion molecules (ICAM-1, PECAM-1, VCAM-1 and P-selectin) were lower in the molsidomine-treated kidneys than in the untreated animals. All these protective effects were not observed after hydralazine administration. In conclusion, intrarenal administration of molsidomine before reperfusion improved renal function and decreased inflammatory responses after I-R.
Rodriguez-Peña
Ana
A
Instituto Reina Sofía de Investigación Nefrológica, Universidad de Salamanca, Salamanca, Spain.
Garcia-Criado
Francisco J
FJ
Eleno
Nelida
N
Arevalo
Miguel
M
Lopez-Novoa
Jose M
JM
D000818:Animals; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008981:Molsidomine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000401:mortality; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013534:Survival
D016207:Cytokines; D020030:Nitric Oxide Donors; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D003404:Creatinine; D008981:Molsidomine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase