Controlling Blood Pressure without Drugs – Developing New Strategies
morbidity. Pre-discharge dose–response testing revealed consistent reductions in systolic blood pressure of ~41mmHg.29
Two- and three-
year data from these studies indicate substantial and sustained (>30mmHg) reductions in patients with resistant hypertension.30 Larger-scale randomised, controlled trials are ongoing to verify potential chronic benefits.
A very recent report addressing potential long-term safety concerns of device implantation in sheep (three to six months post- implantation) and in patients (one to four months post-implantation using duplex ultrasound of the carotid artery) did not reveal evidence of carotid injury or stenosis.31
From a mechanistic point of view, a recent study in 12 patients with an implanted Rheos system indicates that the depressor response to electric field stimulation of carotid sinus baroreflex afferents seems to be mediated mainly through sympathetic inhibition, without negative effects on physiological baroreflex regulation.32 Ultimately, the benefits of blood pressure reduction and neurohormonal inhibition will have to be weighed against the cost and fairly invasive nature of the procedure.
1. 2.
Esler M, Jennings G, Biviano B, et al., Mechanism of elevated plasma noradrenaline in the course of essential hypertension, J Cardiovasc Pharmacol, 1986;8(Suppl. 5):S39–43.
Schlaich MP, Lambert E, Kaye DM, et al., Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and Angiotensin neuromodulation, Hypertension, 2004;43(2):169–75.
3.
Schlaich MP, Kaye DM, Lambert E, et al., Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy, Circulation, 2003;108(5): 560–65.
4.
Hasking GJ, Esler MD, Jennings GL, et al., Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity, Circulation, 1986;73(4): 615–21.
5.
Petersson M, Friberg P, Eisenhofer G, et al., Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure, Eur Heart J, 2005;26(9): 906–13.
6.
Zoccali C, Mallamaci F, Parlongo S, et al., Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease, Circulation, 2002;105(11):1354–9.
7. 8. 9.
Schlaich MP, Socratous F, Hennebry S, et al., Sympathetic activation in chronic renal failure, J Am Soc Nephrol, 2009;20(5):933–9.
Campese VM, Neurogenic factors and hypertension in chronic renal failure, J Nephrol, 1997;10(4):184–7.
Campese VM, Kogosov E, Renal afferent denervation prevents hypertension in rats with chronic renal failure, Hypertension, 1995;25(4 Pt 2):878–82.
10. Campese VM, Kogosov E, Koss M, Renal afferent denervation prevents the progression of renal disease in the renal ablation model of chronic renal failure in the rat, Am J Kidney Dis, 1995;26(5):861–5.
Conclusions and Future Perspectives Hypertension remains a challenging and growing clinical problem. A concerted effort is needed to address this issue, and currently established therapeutic strategies need to be utilised more stringently and aggressively with a particular focus on lifestyle interventions and appropriate pharmacological combination treatment. Nevertheless, there is clearly a need for additional therapeutic strategies, some of which have shown promise in the setting of resistant hypertension, as outlined above. These approaches may require further substantiation in larger and appropriately designed clinical trials, but very clearly establish a crucial role of sympathetic activation in various forms of hypertension. Currently available device-based approaches targeting the sympathetic nervous system may offer novel non-pharmacological approaches, which for now may have particular relevance in uncontrolled patients already on multiple antihypertensive drugs and those intolerant of pharmacological treatment. Given the favourable safety profile and obvious efficacy of the procedure, its application in patients with less severe forms of hypertension with the potential to perhaps cure their hypertension does not appear to be unreasonable. n
11. DiBona GF, Sympathetic nervous system and the kidney in hypertension, Curr Opin Nephrol Hypertens, 2002;11(2): 197–200.
12. DiBona GF, Neural control of the kidney: past, present, and future, Hypertension, 2003;41(3 Pt 2):621–4.
13. Barajas L, Innervation of the renal cortex, Fed Proc, 1978;37(5):1192–1201.
14. Bell-Reuss E, Trevino DL, Gottschalk CW, Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption, J Clin Invest, 1976;57(4):1104–7.
15. Kirchheim H, Ehmke H, Persson P, Sympathetic modulation of renal hemodynamics, renin release and sodium excretion, Klin Wochenschr, 1989;67(17):858–64.
16. Kon V, Neural control of renal circulation, Miner Electrolyte Metab, 1989;15(1–2):33–43.
17. Zanchetti AS, Neural regulation of renin release: experimental evidence and clinical implications in arterial hypertension, Circulation, 1977;56(5):691–8.
18. DiBona GF, Kopp UC, Neural control of renal function, Physiol Rev,1997;77(1):75–197.
19. Kassab S, Kato T, Wilkins FC, et al., Renal denervation attenuates the sodium retention and hypertension associated with obesity, Hypertension, 1995;25(4 Pt 2): 893–7.
20. Grassi G, Seravalle G, Colombo M, et al., Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans, Circulation, 1998;97(20):2037–42.
21. Narkiewicz K, Pesek CA, Kato M, et al., Baroreflex control of sympathetic nerve activity and heart rate in obstructive sleep apnea, Hypertension, 1998;32(6):1039–43.
22. Schobel HP, Fischer T, Heuszer K, et al., Preeclampsia – a state of sympathetic overactivity, N Engl J Med, 1996;335(20):1480–85.
23. Vonend O, Marsalek P, Russ H, et al., Moxonidine treatment of hypertensive patients with advanced renal
failure, J Hypertens, 2003;21(9):1709–17.
24. Strojek K, Grzeszczak W, Gorska J, et al., Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: novel approach to prevent progression of diabetic nephropathy?, J Am Soc Nephrol, 2001;12(3):602–5.
25. Onesti G, Kim KE, Greco JA, et al., Blood pressure regulation in end-stage renal disease and anephric man, Circ Res, 1975;36(6 Suppl. 1):145–52.
26. Krum H, Schlaich M, Whitbourn R, et al., Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study, Lancet, 2009;373(9671):1275–81.
27. Schlaich MP, Sobotka PA, Krum H, et al., Renal sympathetic-nerve ablation for uncontrolled hypertension, N Engl J Med, 2009;361(9):932–4.
28. Lohmeier TE, Irwin ED, Rossing MA, et al., Prolonged activation of the baroreflex produces sustained hypotension, Hypertension, 2004;43(2):306–11.
29. Illig KA, Levy M, Sanchez L, et al., An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial, J Vasc Surg, 2006;44(6): 1213–18.
30. Lovett EG, Schafer J, Kaufman CL, Chronic baroreflex activation by the Rheos system: an overview of results from european and North American feasibility studies, Conf Proc IEEE Eng Med Biol Soc, 2009;2009:4626–30.
31. Sanchez LA, Illig K, Levy M, et al., Implantable carotid sinus stimulator for the treatment of resistant hypertension: local effects on carotid artery morphology, Ann Vasc Surg, 2010;24(2):178–84.
32. Heusser K, Tank J, Engeli S, et al., Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients, Hypertension, 2010;55(3):619–26.
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