PMID: 29760664

Reduced Renal Mass, Salt-Sensitive Hypertension Is Resistant to Renal Denervation

Ionut Tudorancea^1,2,3, Thomas E. Lohmeier⁴, Barbara T. Alexander⁴, Dragos Pieptu⁵, Dragomir N. Serban² and Radu Iliescu^3,4,6,7*

• ¹Cardiology Division Department of Internal Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania
• ²Department of Physiology, Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania
• ³CHRONEX-RD Biomedical Research Center, Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania
• ⁴Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States
• ⁵Department of Plastic and Reconstructive Surgery, Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania
• ⁶Department of Pharmacology, Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania
• ⁷Regional Institute of Oncology, TRANSCEND Research Center, Iași, Romania

Aim: Activation of the sympathetic nervous system is common in resistant hypertension (RHT) and also in chronic kidney disease (CKD), a prevalent condition among resistant hypertensives. However, renal nerve ablation lowers blood pressure (BP) only in some patients with RHT. The influence of loss of nephrons per se on the antihypertensive response to renal denervation (RDNx) is unclear and was the focus of this study.

Methods: Systemic hemodynamics and sympathetically mediated low frequency oscillations of systolic BP were determined continuously from telemetrically acquired BP recordings in rats before and after surgical excision of ∼80% of renal mass and subsequent RDNx.

Results: After reduction of renal mass, rats fed a high salt (HS) diet showed sustained increases in mean arterial pressure (108 ± 3 mmHg to 128 ± 2 mmHg) and suppression of estimated sympathetic activity (∼15%), responses that did not occur with HS before renal ablation. After denervation of the remnant kidney, arterial pressure fell (to 104 ± 4 mmHg), estimated sympathetic activity and heart rate (HR) increased concomitantly, but these changes gradually returned to pre-denervation levels over 2 weeks of follow up. Subsequently, sympathoinhibition with clonidine did not alter arterial pressure while significantly suppressing estimated sympathetic activity and HR.

Conclusion: These results indicate that RDNx does not chronically lower arterial pressure in this model of salt-sensitive hypertension associated with substantial nephron loss, but without ischemia and increased sympathetic activity, thus providing further insight into conditions likely to impact the antihypertensive response to renal-specific sympathoinhibition in subjects with CKD.