“Effects of losartan on the apelin/APJ system and on NF-κB pathway elements in a renal ischemia reperfusion injury (IRI) model”

Giolito, Maria Virginia;et.al.
(2018) LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC) — Location: Mar del Plata, Argentina (14.November.2018)

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Abstract
Apelin is a selective endogenous ligand of APJ receptor, which has closest identity to the angiotensin II type 1 (AT-1) receptor. Nevertheless, the apelin/APJ system has been found to exert opposing actions to angiotensin II/AT-1. Apelin administration improved renal function in an IRI rat model.In previous studies, we found a decreased renal expression of apelin mRNA in IRI. Other work from our laboratory, demonstrated that the renoprotective effects of losartan, in the same model, would be mainly mediated by its anti-inflammatory actions, since the AT-1 blocker treatment decreased TNF-α, IL-6 and IL-1β mRNA levels.The aim of this work was to evaluate the effects of losartan in renal IRI on the expression of apelin, APJ, pNF-kB-p65, A20 (TNF-α-induced protein 3), which functions as NF-kB signaling inhibitor, andToll-like receptor 2 (TLR2), a major NF-kB activator in IRI.Wistar rats underwent sham-surgery (C) or renal 40min-ischemia followed by 24h-reperfusion (IRI). Losartan 80 mg/Kg/day, i.p. was administrated during 3 days prior to IRI (IRI+LOS) or sham-surgery (C+LOS). In cortical tissue, apelin and APJ mRNA expression was analysed by qRT-PCR; and NF-kB, A20 and TLR2 protein expression, by Western blot.The decrease in Apelin mRNA observed in IRI was prevented by losartan (fold changes: C=1; IRI=0.08*; IRI+LOS=0.49#). APJ mRNA levels were diminished in IRI, while losartan increased its expression in C and IRI (C=1; C+LOS=6.68*; IRI=0.08*; IRI+LOS=7.83*#). Both pNF-kB-p65 and TLR2 expression augmented in IRI (*) and decreased in IRI+LOS group (#). IRI-induced increase in A20 expression (*) was inhibited by losartan (#). *p<0.05 vs. C; #p<0.05 vs. IRI.Renal IRI inhibited the expression of apelin/APJ system, which was described to mediate renoprotective actions. Losartan treatment prevented this inhibition. AT-1 antagonism also decreased NF-kB activation, probably by reduction in TLR2 expression and through an A20-independent pathway.
Affiliations
  • Farmacología, Departamento de Ciencias Fisiológicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.

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Giolito, M. V., & et al. (2018). “Effects of losartan on the apelin/APJ system and on NF-κB pathway elements in a renal ischemia reperfusion injury (IRI) model”. LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC), Mar del Plata, Argentina. https://hdl.handle.net/2078.5/267781