Rebuttal from Markus P. Schlaich, Yusuke Sata and Murray D. Esler

Extreme positions are rarely useful and almost invariably hinder rather than facilitate progress in clinical science. Dr Jordan (Jordan, 2014) and Dr Paton (Ratcliffe et al. 2014) and their colleagues seem to share this view and, while making a strong case for each of their points, have provided a reasonably balanced appraisal of the evidence surrounding the interventional approaches for resistant hypertension under debate. Importantly, we seem to share common ground in the view that resistant hypertension is a relevant clinical problem, that non-adherence to prescribed medication is common, that alternative and perhaps device-based therapeutic approaches are needed, and that sympathetic overactivity is a major contributor to the pathophysiology of resistant hypertension thereby providing a logical therapeutic target. Our views differ in how this is best achieved. Dr Jordan elegantly reviews the role of baroreflex circuits in long-term blood pressure (BP) control and how electrical carotid sinus stimulation (CCS) may ameliorate resistant hypertension. While highlighting potential advantages of CCS such as the ability of stimulation adjustment, it becomes clear from his pathophysiological considerations that sympathetic inhibition, specifically suppression of efferent renal sympathetic nerve activity, is an important mediator of CCS-induced depressor responses (Iliescu et al. 2012). Why not target the renal nerves directly when this can be achieved safely with catheter-based approaches (Esler et al. 2010; Bhatt et al. 2014)? Carotid body (CB) denervation is the least developed and investigated approach, which does not negate the physiological relevance of chemoreceptor activation and its role in modulation of both sympathetic nerve activity and blood pressure. Dr Paton promotes the concept of CB tonicity driving sympathetic vasomotor activity chronically, particularly in the scenario of hypertension (Paton et al. 2013). Surgical resection of the CB has been performed to alleviate dyspnoea in patients with obstructive airway disease and coincidentally, a BP reduction was observed in a subgroup of hypertensive patients (Nakayama, 1961). Clearly, recent experimental data is more convincing (McBryde et al. 2013). Nevertheless, evidence for a pivotal role of CB-related mechanisms in human resistant hypertension is weak and the concept far from proven. Major concerns that need to be addressed relate to the potential attenuation or loss of hypoxic ventilatory drive and the potentially serious procedural complications. In keeping with the hypothetical ideals for an interventional approach brought forward by Dr Paton, we would argue that renal denervation remains the most promising therapeutic approach despite the recent setback from a suboptimally conducted clinical trial (Bhatt et al. 2014). Readers are invited to give their views on this and the accompanying CrossTalk articles in this issue by submitting a brief (250 word) comment. Comments may be submitted up to 6 weeks after publication of the article, at which point the discussion will close and the CrossTalk authors will be invited to submit a ‘Last Word’. Please email your comment to journals@physoc.org. Disclaimer: Supplementary materials have been peer-reviewed but not copyedited. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. M. P. Schlaich has received consulting fees, and/or travel and research support from Medtronic, Abbott, Novartis, Servier, Pfizer and Boehringer-Ingelheim. Y. Sata has nothing to disclose. M. D. Esler has received consulting fees, and travel and research support from Medtronic and serves on the scientific advisory boards of Abbott Pharmaceuticals and Medtronic. M. P. Schlaich is supported by an NHMRC Research Fellowship.