J Physiol 592.18 (2014) p 3945 3945

The

Jou

rnal

of

Phys

iolo

gy

C R O S S TA L K

Rebuttal from Jens Jordan

Jens JordanInstitute of Clinical Pharmacology,Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany

Email: jordan.jens@mh-hannover.de

The new interventional treatmentsdiscussed in this CrossTalk debate addressfundamental physiological mechanismsregulating autonomic nervous systemactivity and blood pressure, namelyrenal innervation, peripheral chemo-receptors, or carotid baroreflexes. Thesolid physiological rationale behindcatheter-based renal denervation (Ratcliffeet al. 2014) and carotid chemoreceptordenervation/modulation (Schlaich et al.2014) has been reviewed by a groupof internationally recognized experts inthe field. There is not much I couldadd. I would argue that catheter-basedrenal denervation, carotid chemoreceptordenervation/modulation and electricalcarotid sinus stimulation deserved toundergo rigorous clinical testing. However,the road from a good idea to an effectivetreatment that can be incorporated intoroutine clinical care is a long one.

Both Ratcliffe et al. (2014) and Schlaichet al. (2014) suggest that silver bulletinterventional cures are unlikely. I couldnot agree more. Interventional treatmentsfor resistant primary hypertension maysimply fail for technical reasons. Thetechnology ought to be improved andwe should find ways to identify technicalfailure early on. More importantly, thereare pathophysiological reasons why notall patients will respond to a treatmentlowering blood pressure through solemanipulation of sympathetic nervoussystem activity. The statement by Schlaichet al. (2014) that sympathetic activationis the hallmark of arterial hypertensionis somewhat misleading. Instead, thecontribution of sympathetic activity toarterial hypertension appears to varyfrom patient to patient. We applied

pharmacological ganglionic blockade,which acutely abolishes sympathetic andparasympathetic efferent activity, to gaugeautonomic nervous system contributionsto primary hypertension in an earlierstudy (Jordan et al. 2002). In somepatients, blood pressure remained elevatedduring ganglionic blockade. Similarly, inrare patients with near complete loss ofperipheral autonomic nerves and supinehypertension, blood pressure remainselevated during ganglionic blockade(Shannon et al. 2000). Sympatheticinhibition cannot control blood pressure inall patients.

The column heading in the paper bySchlaich et al. stating that catheter-basedrenal denervation is safe and effective maybe a little too optimistic. The fact that theprocedure did not lower blood pressure inSimplicity-3 compared to rigorous controlscannot be neglected. In the past, Europeanregulations permitted approval of devicesin the absence of true efficacy data. Thecompany producing a device had to showthat operator and patient are not harmedand that the device serves its stated purpose.Data from smaller-scaled studies withouta rigorous control group were sufficientfor the agencies. Arterial stents served thestated purpose abolishing atheroscleroticrenal artery stenosis. However, they failedmiserably in controlling hypertension(Cooper et al. 2014). The scientificcommunity should be smarter by nowand not accept treatments that have notbeen proven useful in sufficiently largeand well-controlled clinical trials. Finally,procedures should be tested with thesame rigor as tablet-based interventions.Simplicity-3 (Bhatt et al. 2014) wasexemplary in that regard.

Call for comments

Readers are invited to give their views on thisand the accompanying CrossTalk articles in thisissue by submitting a brief (250 word) comment.Comments may be submitted up to 6 weeks afterpublication of the article, at which point thediscussion will close and the CrossTalk authors

will be invited to submit a ‘Last Word’. Pleaseemail your comment to journals@physoc.org.

References

Bhatt DL, Kandzari DE, O’Neill WW,D’Agostino R, Flack JM, Katzen BT, Leon MB,Liu M, Mauri L, Negoita M, Cohen SA, OparilS, Rocha-Singh K, Townsend RR & Bakris GL;SYMPLICITY HTN-3 Investigators (2014). Acontrolled trial of renal denervation forresistant hypertension. N Engl J Med 370,1393–1401.

Cooper CJ, Murphy TP, Cutlip DE, Jamerson K,Henrich W, Reid DM, Cohen DJ, MatsumotoAH, Steffes M, Jaff MR, Prince MR, Lewis EF,Tuttle KR, Shapiro JI, Rundback JH, MassaroJM, D’Agostino RB Sr & Dworkin LD (2014).Stenting and medical therapy foratherosclerotic renal-artery stenosis. N Engl JMed 370, 13–22.

Jordan J, Tank J, Hohenbleicher H, Toka HR,Schroeder C, Sharma AM & Luft FC (2002).Heterogeneity of autonomic regulation inhypertension and neurovascular contact.J Hypertens 20, 701–706.

Ratcliffe LEK, Pijacka W, McBryde FD, AbdalaAP, Moraes DJ, Sobotka PA, Hart EC,Narkiewicz K, Nightingale AK & Paton JFR(2014). CrossTalk opposing view: Whichtechnique for controlling resistanthypertension? Carotid chemoreceptordenervation/modulation. J Physiol 592,3941–3944.

Schlaich MP, Sata Y & Esler MD (2014).CrossTalk opposing view: Which techniquefor controlling resistant hypertension? Renalnerve ablation. J Physiol 592, 3937–3940.

Shannon JR, Jordan J, Diedrich A, Pohar B,Black BK, Robertson D & Biaggioni I (2000).Sympathetically mediated hypertension inautonomic failure. Circulation 101,2710–2715.

Additional information

Competing interests

None declared.

Funding

None declared.

C© 2014 The Authors. The Journal of Physiology C© 2014 The Physiological Society DOI: 10.1113/jphysiol.2014.279711