(Hypertension. 1995;25:878-882.)
© 1995 American Heart Association, Inc.
Articles |
Renal Afferent Denervation Prevents Hypertension in Rats With Chronic Renal Failure
From the Division of Nephrology, Department of Medicine, University of Southern California, Los Angeles.
Correspondence to Vito M. Campese, MD, Division of Nephrology, LAC/USC Medical Center, 2025 Zonal Ave, Los Angeles, CA 90033.
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 
-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.
Key Words: afferent pathways • hypertension, renal • kidney failure • denervation
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