Importance of renal sympathetic tone in the development of DOCA-salt hypertension in the rat.

TLDR

Acute sympathetic activation produces markedly greater renal vasoconstriction than in other vascular beds. The study tested whether attenuating renal sympathetic tone would delay the onset of DOCA‑salt hypertension in rats. Renal denervation was performed on 5‑week‑old uninephrectomized Sprague‑Dawley rats one week before initiating DOCA‑salt treatment. Denervation postponed hypertension until day 17, preserved early sodium excretion, but later caused a rapid blood‑pressure rise and loss of sodium excretion, accompanied by a threefold rise in renal norepinephrine suggesting reinnervation, indicating that renal sympathetic tone is required for DOCA‑salt hypertension.

Abstract

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.