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

Elizabeth Barbosa De Oliveira Sales, Eduardo Colombari, Ana Paula Abdala Sheikh, Ruy R Campos, Julian F R Paton*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

41 Citations (Scopus)
388 Downloads (Pure)


Our knowledge of mechanisms responsible for both the development and maintenance of hypertension remains incomplete in the Goldblatt model (two kidney one clip, 2K1C). We tested the hypothesis that elevated sympathetic nerve activity (SNA) occurs before the onset of hypertension in 2K1C rats considering the time course of increase in SNA in relation to the onset of the hypertension is determined. We used a decorticated in situ working heart-brainstem preparation of male Wistar rats comprising: SHAM (n = 7), three 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; 2K1C-N: 74 ± 3 vs SHAM: 60 ± 2 mmHg, p< 0.05). The SNA was elevated significantly in both 2K-1C groups (2K1C-H: 47.7 ± 6.1; 2K1C-N: 32.8 ± 2.8 vs SHAM: 20.5 ± 2.5 μV, p< 0.05) due to its increased respiratory modulation; the chemoreflex was augmented and baroreflex depressed. Pre-collicular transection reduced SNA in all groups (2K1C-H: -32.5 ± 7.5, 2K1C-NH: -48 ± 6.9 vs SHAM: -13.2 ± 1%, p< 0.05). Subsequent medullary-spinal cord transection abolished SNA in both SHAM and 2K1C-N but only decreased it by 57± 5.5% in 2K1C-H. Thus, SNA is raised prior to hypertension onset by the 3rd 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 when after hypertension has developed.
Original languageEnglish
Pages (from-to)67-80
Number of pages14
JournalExperimental Physiology
Issue number1
Early online date14 Dec 2015
Publication statusPublished - 1 Jan 2016


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