Sympathetic overactivity occurs before hypertension in the two-kidney, one-clip model.

Our knowledge of mechanisms responsible for both the development and the maintenance of hypertension remains incomplete in the Goldblatt (two-kidney, one-clip; 2K1C) model. We tested the hypothesis that elevated sympathetic nerve activity (SNA) occurs before the onset of hypertension in 2K1C rats, considering the time course of the increase in SNA in relationship to the onset of the hypertension. We used a decorticated in situ working heart-brainstem preparation of three groups of male Wistar rats, namely sham-operated animals (SHAM, n = 7) and animals 3 weeks post-2K1C, of which some were hypertensive (2K1C-H, n = 6) and others normotensive (2K1C-N, n = 9), as determined in vivo a priori. Perfusion pressure was higher in both 2K1C groups (2K1C-H, 76 ± 1 mmHg; 2K1C-N, 74 ± 3 mmHg; versus SHAM, 60 ± 2 mmHg, P < 0.05). The SNA was significantly elevated in both 2K1C groups (2K1C-H, 47.7 ± 6.1 μV; 2K1C-N, 32.8 ± 2.8 μV; versus SHAM, 20.5 ± 2.5 μV, P < 0.05) owing to its increased respiratory modulation; the chemoreflex was augmented and baroreflex depressed. Precollicular transection reduced SNA in all groups (2K1C-H, -32.5 ± 7.5%; 2K1C-NH, -48 ± 6.9%; versus SHAM, -13.2 ± 1%, P < 0.05). Subsequent medullary spinal cord transection abolished SNA in both SHAM and 2K1C-N groups, but decreased it by only 57 ± 5.5% in 2K1C-H preparations. Thus, SNA is raised before the onset of hypertension, by the third week after renal artery clipping, and this originates, in part, from its enhanced respiratory modulation. Spinal circuits contribute to the elevation of SNA in the 2K1C model, but only after hypertension has developed.