Altered urinary sodium excretion response after central cholinergic and adrenergic stimulation of adult spontaneously hypertensive rats.

In this study, we hypothesized that blunting of the natriuresis response to intracerebroventricularly (i.c.v.) microinjected cholinergic and adrenergic agonists is involved in the development of hypertension in spontaneously hypertensive rats (SHR). We evaluated the effect of i.c.v. injection of cholinergic and noradrenergic agonists, at increasing concentrations, and of muscarinic cholinergic and α1 and α2-adrenoceptor antagonists on blood pressure and urinary sodium handling in SHR, compared with age-matched Wistar Kyoto rats (WR). We confirmed that CCh and NE microinjected into the lateral ventricle (LV) of conscious rats leads to enhanced natriuresis. This response was associated with increased proximal and post-proximal sodium excretion accompanied by an unchanged rate of glomerular filtration. We showed that cholinergic-induced natriuresis in WR and SHR was attenuated by previous i.c.v. administration of atropine and was significantly lower in the hypertensive strain than in WR. In both groups the natriuretic effect of injection of noradrenaline into the LV was abolished by previous local injection of an α1-adrenoceptor antagonist (prazosin). Conversely, LV α2-adrenoceptor antagonist (yohimbine) administration potentiated the action of noradrenaline. The LV yohimbine pretreatment normalized urinary sodium excretion in SHR compared with age-matched WR. In conclusion, these are, as far as we are aware, the first results showing the importance of interaction of central cholinergic and/or noradrenergic receptors in the pathogenesis of spontaneous hypertension. These experiments also provide good evidence of the existence of a central adrenergic mechanism consisting of α1 and α2-adrenoceptors which works antagonistically on regulation of renal sodium excretion.

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.