Renal afferent denervation prevents hypertension in rats with chronic renal failure.

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 alpha-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.(ABSTRACT TRUNCATED AT 250 WORDS)