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

Abstract

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.

Dexamethasone Causes Hypertension in Rats Even Under Chemical Blockade of Peripheral Sympathetic Nerves

“…However, in this investigation, the absence of renal nerves did not prevent DEX-induced hypertension. These results are consistent with earlier reports where RDNX was not able to eliminate blood pressure elevations in the Dahl NaCl-sensitive rats (Wyss et al, 1987) and salt-sensitive-related hypertension (Foss et al, 2018; Tudorancea et al, 2018). Actually, RDNX exacerbates the response to DEX (Figure 1B); that may be associated with an increase in vascular reactivity.…”

Prenatal cold exposure causes hypertension in offspring by hyperactivity of the sympathetic nervous system

“…Renal sympathetic denervation of 11-week-old rats was performed by chemical ablation as described previously [20,21]. Briefly, after anesthetizing the rats with pentobarbital (50 mg/kg, i.p.…”

Device-Based Neuromodulation for Resistant Hypertension Therapy

“…For example, RDN in rats did not attenuate HT caused by chronic ANG II infusion or by salt loading and reduced kidney mass. 85,89 In rabbits, RSNA is suppressed in ANG II HT and RDN does not attenuate the HT. 86,87 In dogs, RSNA is not increased in ANG II HT 18,22 and RDN did not substantially ameliorate HT caused by renal artery stenosis 91,92 or by chronic aldosterone infusion.…”

“…Previous studies in experimental animals have shown that RDN has little effect on BP in models of HT with normal/low sympathetic activity such as HT induced by chronic infusion of ANG II or aldosterone, renal artery stenosis, or salt loading in animals with reduced nephron numbers. 62,85,[87][88][89]137 Secondary analyses of data from SYMPLICITY HTN-3 also suggest that RDN may be less effective in patients who have volume-dependent forms of HT. 63 In contrast, RDN has been shown to be highly effective in reducing BP in obesity-induced HT which is associated with increased RSNA and may account for 65-75% of the risk for primary HT as well being a major contributor to treatment resistant HT.…”