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.
Highlights
The frequent association between chronic kidney disease (CKD) and treatment resistant hypertension (RHT) leads to a high incidence of adverse renal and cardiovascular outcomes, reflecting the likely, not well studied, reciprocal potentiation of these conditions on the severity of the hypertension and its progression (Calhoun et al, 2008; De Beus et al, 2015; Rossignol et al, 2015; Thomas et al, 2016; Wolley and Stowasser, 2016)
After returning the rats to LS in preparation for unilateral nephrectomy and partial surgical ablation of the remaining kidney, all variables returned to values indistinguishable from control except mean arterial pressure (MAP), as indicated above
(3) Indirect measures of sympathetic activity are consistent with these blood pressure (BP) responses in that they indicate that sympathetic activity is suppressed during reduced renal mass (RRM) and HS
Summary
The frequent association between chronic kidney disease (CKD) and treatment resistant hypertension (RHT) leads to a high incidence of adverse renal and cardiovascular outcomes, reflecting the likely, not well studied, reciprocal potentiation of these conditions on the severity of the hypertension and its progression (Calhoun et al, 2008; De Beus et al, 2015; Rossignol et al, 2015; Thomas et al, 2016; Wolley and Stowasser, 2016). A neglected area of investigation is the impact of CKD on the antihypertensive response to RDNx. Despite initial encouraging results from small-scale studies (Schlaich et al, 2013; Wallbach et al, 2014; Beige et al, 2015; Ott et al, 2015; Kiuchi et al, 2016; Hering et al, 2017), the efficacy and safety of RDNx in patients with RHT and CKD remain uncertain, as large clinical trials using this non-pharmacological approach for BP control have excluded patients with impaired renal function, for fear of worsening renal injury (Symplicity HTN-2 Investigators Esler et al, 2010; Bhatt et al, 2014; De Beus et al, 2014; Persu et al, 2014; Grassi et al, 2015; Wolley and Stowasser, 2016)
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