By Paige VonAchen
Ten percent of adults suffer from “resistant” hypertension that is unresponsive to antihypertension drugs for unknown reasons.1 Millions of dollars have been poured into research on the causes of and treatments for hypertension.
In studying factors that contribute to high blood pressure, researchers have observed that the sympathetic nervous system (the “fight” part of our body’s “fight-or-flight” response) plays a major role. Elevated sympathetic nervous system activity results in constricted blood vessels and an increased heart rate. With the heart pumping more blood, and a narrower vessel for the blood to flow through, the pressure inside the circulatory system (the system that conducts blood through the body) increases.2
This understanding has led to today’s antihypertension drugs which systemically decrease the activity of the sympathetic nervous system. Patients who take these drugs experience a decrease in blood pressure and are at a lower risk for cardiovascular disease.
Diving deeper into these mechanisms, it has been found that along with the sympathetic nervous system, the renin-angiotensin pathway in the kidney also increases
blood pressure. This works through the following series of events: in response to low blood flow in the kidneys, the juxtaglomerular cells in these organs release renin, a protein. This molecule consequently helps to convert another molecule, angiotensinogen, into angiotensin I, and finally angiotensin II. Angiotensin II is a potent vasoconstrictor, which increases blood pressure in a similar manner as the sympathetic nervous system.
In the 1930s, in order to reduce patients’ blood pressure, doctors would surgically remove the nerves that detect blood flow in the kidneys. However, these practices were high risk, and with the development of antihypertension drugs, the procedure was eventually phased out. As hypertension rates continue to rise – likely due to an increase in sedentary lifestyles in certain populations – and medical technologies progress, there has been a renewed interest in finding solutions that are as direct as the original nerve removal surgeries, albeit less invasive.3
Fast-forward to today, and we find the largest medical device companies racing to develop “renal denervation” technologies that safely ablate, or burn, these kidney nerves.
What is renal denervation? It is a non-invasive catheter-based procedure that delivers low-level radiofrequency energy through the renal artery wall to the surrounding nerves. It consists of a device similar to that pictured in Figure 1. The wire-like part of the instrument is inserted through a patient’s circulatory system into the renal artery (Figure 2). The probe at of the end of the wire (Figure 3) effectively ablates surrounding nerves with radio frequency energy. This inhibits the renin-angiotensin pathway that would normally increase blood pressure. The result is a decrease in vasoconstriction and a decrease in the patient’s blood pressure.3 If medical compaines can get these new renal denervation devices approved by the Food and Drug Administration, analysts estimate the hypertension-treating device market to be at about $2.8 billion dollars by 2020.4
Medtronic, the world’s largest medical device company and the leader in the renal denervation race, has gone through three clinical trials testing its “Symplicity” device. The first two trials showed that the procedure safely denervates the kidney and provides substantial, sustained reductions in blood pressure in humans.
Unfortunately, their latest and most extensive study has shown no significant differences between those treated with the device and the control group.5 However, a recent post hoc analysis of the trial suggested that there were confounding factors that may have impacted the final results.6
Despite the potential possibilities of success with renal denervation, doctors and patients should not treat it as the holy grail of hypertension treatment. In addition to this procedure, doctors should also focus on preventative measures, including a healthy diet and exercise. However, not all cases of blood pressure and cardiovascular disease are due to lifestyle. People may be genetically predisposed to cardiovascular disease.
Will renal denervation technology be the solution to the world’s rising cardiovascular disease problem? Only time will tell. As companies and research groups continue to hash out the kinks with this technology, patients with resistant hypertension wait anxiously for the procedure to be available to the general public. ∎
1. Hypertension. (n.d.). Web. April 29, 2015, from http://www.world-heart-federation.org/cardiovascular-health/cardiovascular-disease-risk-factors/hypertension/
2. Guyenet, P. (n.d.). The Sympathetic Control Of Blood Pressure. Nature Reviews Neuroscience, 335-346.
3. Renal sympathetic denervation for treatment of resistant hypertension. (n.d.). Web. April 29, 2015, http://www.mayoclinic.org/medical-professionals/clinical-updates/general-medical/renal-sympathetic-denervation-treatment-resistant-hypertension
4. Renal Denervation – The Next Big Thing in Medical Devices. (n.d.). Web. April 29, 2015, from http://www.fiercemedicaldevices.com/special-reports/renal-denervation-next-big-thing-medical-devices
5. Bhatt, D., Kandzari, D., O’neill, W., D’agostino, R., Flack, J., Katzen, B., . . . Bakris, G. (n.d.). A Controlled Trial of Renal Denervation for Resistant Hypertension. New England Journal of Medicine, 140329050012001-140329050012001.
6. Kandzari, David E., Bhatt, Deepak L, Brar, Sandeep, Devireddy, Chandan M., Bakris., George L (n.d.) Predictors of blood pressure response in the Symplicity HTN-3 Trial. European Heart Journal., 2015 Jan 21;36(4):219-27