NDT Advance Access published online on July 1, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn368
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Renal contribution to thermolability in rats: role of renal nerves
Disciplina de Medicina Interna, Departamento de Clínica Médica, Laboratório de Metabolismo Hidro-Salino, Núcleo de Medicina e Cirurgia Experimental and Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13083-592 Campinas, SP, Brazil
Correspondence and offprint requests to: José A. R. Gontijo, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13083-592 Campinas, SP, Brazil. Tel: +55-19-3521 8924; Fax: +55-19-3521 8925; E-mail: gontijo{at}fcm.unicamp.br
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Abstract |
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Background. Body temperature is closely regulated via the integration of a number of mechanisms, the study of which has been greatly assisted by the exploitation of comparative physiology. Previous studies have demonstrated that chronic renal failure patients have significantly lower body temperatures than healthy subjects when artifacts from circadian changes were taken into consideration. We hypothesize that the blunting of renal sensory neurons after kidney partial ablation may contribute to the lack of suppression of sympathetic efferent outflow towards BAT, modifying the glucose metabolism signaling pathway, UCP 1 expression and liver mitocondrial respiratory chain activity.
Methods. To evaluate the influence of renal mass reduction, renal denervation and chronic deafferentation by capsaicin on thermoregulation, glucose metabolism, UCP1 expression and liver mitocondrial respiration, was used respectively, the blocking of heat dissipation by thermoneutral body water immersion, the oxygen consumption by Clark-type electrode, and western blot method.
Results. The study confirmed that, following 5/6 nephrectomy, the basal core temperature of rats was significantly lower than that of control animals when maintained in a thermoneutral body water immersion recipient, as compared to controls. Additionally, we demonstrated that exposure of bilateral renal denervated or of renal chronic capsaicin-treated rats to a similar experimental protocol results in a fast and high rise in rectal temperature response, and this is associated with a significant increase in the basal serine phosphorylation and protein levels of Akt and protein levels of UCP1. This was observed despite unchanged liver mitochondria respiratory control and ADP/O ratios in 5/6 Nx, as well as DNx, when compared to control mitochondria.
Conclusions. Speculatively, it may be suggested that one of the renal sensory nerve signal defects associated with decreased kidney energy generation, induced by kidney ablation, may result in an inability to control the body temperature.
Keywords: kidney; partial nephrectomy; temperature regulation; UCP
Received for publication: 17. 7.07
Accepted in revised form: 9. 6.08