Renal contribution to thermolability in rats: role of renal nerves.

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.

Effects of NH4Cl intake on renal growth in rats: role of MAPK signalling pathway.

BACKGROUND: There is a surprising lack of experimental data on the mechanisms of NH4Cl-induced chronic metabolic acidosis which causes kidney hypertrophy. The NH4Cl treatment results in an absolute increase in kidney mass. Despite findings to indicate a close interaction between NH4Cl-induced chronic metabolic acidosis and renal enlargement, the role of the stimulated serine kinase cascade, mediated by the stepwise activation of extracellular signal-regulated kinase (ERK) signalling, on kidney hypertrophy has not yet been investigated. METHODS: To test this hypothesis, the present study was undertaken to further explore the possible involvement of mitogen-activated protein kinase (MAPK) signalling pathway in renal growth in chronic NH4Cl-treated rats by western blot analysis. RESULTS: Our major findings are as follows: (1) Urinary sodium excretion significantly increased during the early phases of NH4Cl-induced acidosis, (2) This occurrence is associated with sustained renal hypertrophy, and (3) sustained basal phosphorylation of IRS-1, Shc, and MAPK/ERKs in acidotic kidneys. CONCLUSIONS: The present study confirms that NH4Cl-induced acidosis causes disturbances in renal sodium handling. In addition, these findings demonstrate a sustained pre-stimuli activation of kidney MAPK/ERKs signalling pathways in the NH4Cl-treated rats that may correlate with an increased rate of kidney hypertrophy and a transient renal tubule inability to handle sodium. Thus, the altered renal electrolyte handling may result from a reciprocal relationship between the level of renal tubule metabolic activity and ion transport. In addition, the study shows that the appropriate regulation of tyrosine kinase protein phosphorylation, and its downstream signal transduction pathway, plays an important role on renal growth in the NH4Cl-treated rats.