Nonpharmacological treatments for hypertension

One of the dominant mechanisms in the pathophysiology of essential hypertension is sympathetic nervous system overactivity [1]. Many forms of experimental hypertension are mediated via the sympathetic nervous system [2]. The first successful pharmacologic denervation of sympathetic control was by the hexamethonium drugs [3]. This rapidly led to the early therapeutic applications of ganglionic blockade in the treatment of malignant hypertension. Surgical sympathectomy was also an early treatment for hypertension [4]. A more physiological method is to stimulate the baroreflex, which can be depressed in older people [5], probably from atheroma and/or stiffening of the carotid sinus area. In this issue of the Journal of Hypertension there is an important update on the use of carotid baropacing as a more physiological treatment for hypertension: from the Maastricht group who have done so much to develop a new and more sustainable method for chronic stimulation of the carotid baroreceptors [6]. This is not an entirely novel technique, as there had been several earlier attempts to do this [7], but these largely failed to reduce blood pressure (BP) consistently in the longer term, mainly because of the fact that electrodes wrapped around the carotid sinus nerve damaged the nerve directly, or interfered with the blood supply to the nerve. The new technique avoids this pitfall by placing the stimulating electrodes directly on the sinuses with glue rather than stitches, so minimizing trauma to the afferent nerves [8] (the receptors themselves are largely at the junction of the arterial muscle media and the adventitia). These recent studies from the group of de Leeuw and colleagues in 45 patients with drug-resistant hypertension from nine clinical centres in the Netherlands and Switzerland using the Rheos system show that the effect of an acute stop/restart of the stimulation was clearly present at 4 and 13 months after implantation, in response to increasing the stimulation voltage [6]. Later studies (personal communication, de Leeuw, 1 June 2012) show that the chronic response to stimulation was sustained up to 4 years in both clinic and ambulatory SBP. What is quite surprising at first sight is that the reduction in BP appears to be even greater in later years than initially. This implies that there is neither any long-term damage to the carotid, nor any habituation to the stimulation. A few individuals were not able to tolerate the discomfort of the higher voltages necessary for more effective reduction in BP. Nevertheless, the degree of long-term BP reduction was very impressive: around 40–50 mmHg SBP, and 20–30 mmHg DBP at 4 years. This important article [6], focused on the use of carotid stimulation, clarifies in humans the fact that the arterial baroreflex controls the level of BP over the long term, and is not merely concerned with short-term BP variability, as was originally postulated for many years by Guyton and colleagues [10,11] on the basis of a misinterpretation of their own data from isolated baroreceptor denervated dogs [12]. Of course this new article by Alnima et al.[6] in the current journal, which is focused on the arterial baroreflex, does not mention the elephant in the room – namely the exciting recent data from Esler's group in Australia [1,2,7,9] – concerning equally large falls in BP to those seen with baroreflex stimulation. The renal denervation was achieved via a specially developed catheter introduced percutaneously from the femoral artery. This is a much simpler and less invasive procedure than the surgery and implanted bulky generator used for the baroreceptor stimulation technique. The very simplicity of the renal denervation procedure guarantees that this will be rapidly taken up, but by whom? My guess is that which specialist does the renal denervation – cardiologist, radiologist or nephrologist – will vary from centre to centre, depending on local expertise. The genie is clearly out of the bottle, so that this may need careful regulation. But the situation is further complicated by the more recent development of a simpler unilateral carotid stimulator ([9] and de Leeuw, personal communication). The original bilateral method could be programmed externally for single or dual carotid stimulation. Surprisingly, it turned out that unilateral stimulation was similarly effective as bilateral stimulation. This halved the size of the stimulator and greatly reduced the time and complications of implantation. In addition, it has been found that a simple disc can be glued to the sinus, rather than the original sinus wrap-around multiple electrode design. For the renal denervation technique, the original Medtronic/Ardian catheter is intensively pursued by around 30 new modifications which are in the course of clinical testing, one of which has a basket-like collection of five electrodes [13] which might obviate any problems caused by the Medtronic catheter's potential lack of adherence to the endothelial surface of the sinus wall – so watch this space! In conclusion, these two new techniques for the nonpharmacologic treatment of severe hypertension seem equally effective, but at present they are expensive and rightly restricted to investigational use. But they will become much less expensive if applied to more people and further simplified. In the long run it seems likely that we will need a trial, which randomizes seriously drug-resistant hypertension to one or other of these techniques. Ideally, this should be a four-cell factorial design: renal denervation, carotid stimulation, both or neither. This would have to be funded by a public body such as the National Institutes of Health, as it will be too expensive and risky for a device manufacturer. In addition, I apologize for the several references to personal communications from the Maastricht group, but over 2 years ago I had the privilege of examining the thesis of Ingrid Scheffers, which was the basis of the early studies of baropacing there. It is interesting to see how much and how fast this has developed. We live in exciting times! ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.