Hypertension, Vol 2, 266-273, Copyright © 1980 by American Heart Association
RE Katholi, AJ Naftilan and S Oparil
In many experimental models, acute increases in sympathetic nervous system
activity produce disproportionately greater vasoconstriction in the renal
vascular bed than occurs in most other vascular beds. Since increased
sympathetic nervous system activity has been implicated in the pathogenesis
of DOCA-salt hypertension in the rat, we hypothesized that an attenuation
of renal sympathetic tone would delay the development of this form of
hypertension. Renal denervation was carried out in 5-week-old
uninephrectomized male Sprague-Dawley rats 1 week before beginning
DOCA-salt treatment. Systolic blood pressures using the tailcuff method in
32 sham-operated rats were significantly (p less than 0.05) elevated above
control by Day five (115 +/- 3 vs 128 +/- 3 mm Hg) of DOCA-salt
administration and continued to rise, reaching a plateau by Day 21 (192 +/-
5 mm Hg). In contrast, DOCA-salt administration in 32 renal denervated rats
did not result in a significant elevation of blood pressure above control
until Day 17 (121 +/- 3 vs 135 +/- 3 mm Hg, p less than 0.05). During the
first 2 weeks of DOCA-salt treatment, fractional urinary sodium excretion
was significantly greater (p less than 0.05) in renal denervated rats than
in sham animals. During the third week of DOCA-salt administration, renal
denervated rats had a rapid rise in blood pressure and a fall in fractional
urinary sodium excretion to the level of the sham-operated animals.
Coincident with the development of hypertension was a threefold increase in
renal norepinephrine content (5.3 +/- 0.4 ng/g on Day 14 vs 17.7 +/- 3.0
ng/g on Day 24, p less than 0.01), suggesting reinnervation. These data
suggest that increased renal sympathetic tone in the DOCA-salt rat
facilitates sodium retention and is necessary for the development of the
hypertension.
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Importance of renal sympathetic tone in the development of DOCA-salt hypertension in the rat
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