Renal Afferent Denervation Prevents Hypertension in Rats With Chronic Renal Failure

Abstract

Abstract Increased activity of the sympathetic nervous system has been described in chronic renal failure, but its role in the genesis and maintenance of hypertension associated with this condition has not been established. The kidney has an intense network of chemoreceptors and baroreceptors that send impulses to the brain. To what extent activation of these receptors by the scarred kidney or the uremic milieu may contribute to this model of hypertension is unknown. In the present study, we evaluated the effect of bilateral dorsal rhizotomy on the development of hypertension and neuroadrenergic activity in the anterior, lateral, and posterior hypothalamic nuclei, in the locus ceruleus, and in the nucleus tractus solitarius of Sprague-Dawley rats that underwent 5/6 nephrectomy or were sham operated. Neuroadrenergic activity was determined by calculating norepinephrine turnover rate after inhibition of norepinephrine synthesis with α-methyl-dl-p-tyrosine methyl ester hydrochloride. The endogenous norepinephrine concentration was significantly greater in the posterior and lateral hypothalamic nuclei and the locus ceruleus, but not in the nucleus tractus solitarius, and the anterior hypothalamic nuclei of uremic rats compared with control rats. In rats with chronic renal failure and sham rhizotomy, the turnover rate of norepinephrine in the posterior (15.3±1.61 nmol · g−1· h−1) and lateral hypothalamic nuclei (11.7±2.12 nmol · g−1· h−1) and in the locus ceruleus (26.6±2.42 nmol · g−1· h−1) was significantly faster (P<.01) than in rats with renal failure and dorsal rhizotomy (4.1±0.51, 4.7±0.77, and 5.1±1.13 nmol · g−1· h−1, respectively) or control animals with or without rhizotomy. The turnover rate of norepinephrine in the anterior hypothalamic nuclei and the nucleus tractus solitarius was not different among the three groups of rats. These studies demonstrated that in rats with chronic renal failure, bilateral dorsal rhizotomy in the dorsolateral aspect of the vertebral bodies (T10 to L2) prevents in large part the development of hypertension and the increase in norepinephrine turnover rate in the posterior and lateral hypothalamic nuclei and the locus ceruleus. The data provide evidence that renal afferent impulses from the kidneys of rats with chronic renal failure may activate areas of the brain involved in the neuroadrenergic regulation of blood pressure. This mechanism may contribute to the genesis of hypertension in uremic rats.