**14. Baroreflex activation**

The influence of the baroreflex in the control of the BP has been known for centuries. As long ago as 1799, Parry described for the first time in humans that carotid compression not only produced bradycardia but also hypotension. (Doumas, Guo & Papademetriou., 2009) When there is elevation in BP the baroreceptors are activated to decrease sympathetic outflow to the heart, kidneys, and peripheral arteries as well as it increases the parasympathetic tone in the heart. The result is a decrease in peripheral vascular resistance, heart rate and BP. The decrease in renal sympathetic tone reduces RAAS activity with resulting reduction of salt and water retention by the kidney and a decrease in the Ang II. The decrease in vasopressin arginine secretion observed during the increase in baroreceptor activity helps reduce systemic vasoconstriction and renal retention of water. That is why the regulatory role of arterial baroreceptors in the fluctuations of BP short term and sustained elevations in BP are well established. (Guyton et al., 1972)

On the other hand, there is accumulating evidence suggesting that sympathetic nerve activity plays an important role in the pathogenesis of essential hypertension. The findings indicate that sympathetic arousal is especially pronounced in patients who are difficult to control BP as in isolated systolic hypertension, hypertension associated with obesity and obstructive sleep apnea and in those with a non-dipper of BP pattern.

Early studies on the role of the baroreflex in the control of BP, were held in 1950 in dogs to which electrical stimulation of the carotid sinus was applied, showing significant decrease in BP in normotensive and hypertensive animals. (Morrissey, Brookes & Cooke., 1953) These data suggest that the baroreflex is important in chronic hypertension and renal sympathetic inhibition with an increase in natriuresis what could be the mechanism by which the baroreflex is involved in controlling long term BP.

After overcoming years of many technical difficulties, Tuckman implanted stimulators in both carotid sinuses allowing the regulation of stimulus achieving a BP reduction without adverse effects for a period of 2 to 18 months. (Tuckman et al., 1972) Other researchers conducted studies with similar results. (Parsonnet et al., 1969, Rothfeld et al., 1969, Brest, Wiener & Bachrach., 1972) Currently several studies are underway with a Rheos device that produces chronic electrical stimulation of the carotid sinuses (CVRx, MN, USA): European and U.S. study Feasibility and Rheos Pivotal trial. (Fig.2)

Rheos system includes a small pulse generator that is implanted under the collarbone, two thin wires that are implanted in the left and right carotid arteries and are connected to the pulse generator and Rheos programmer system: an external device used by physicians for non-invasive control of the energy delivered by the generator to the overhead wires. In the Device Based Therapy of Hypertension study (Debut-HT), 16 patients completed 2 years of

Also, They noted a significant decrease in aldosterone level,while there was no decrease in

Although the treatment is minimally invasive and presented no apparent complications, it is reserved only for patients with resistant hypertension unresponsive to adequate medical treatment. However randomized studies should be conducted with a larger population and

The influence of the baroreflex in the control of the BP has been known for centuries. As long ago as 1799, Parry described for the first time in humans that carotid compression not only produced bradycardia but also hypotension. (Doumas, Guo & Papademetriou., 2009) When there is elevation in BP the baroreceptors are activated to decrease sympathetic outflow to the heart, kidneys, and peripheral arteries as well as it increases the parasympathetic tone in the heart. The result is a decrease in peripheral vascular resistance, heart rate and BP. The decrease in renal sympathetic tone reduces RAAS activity with resulting reduction of salt and water retention by the kidney and a decrease in the Ang II. The decrease in vasopressin arginine secretion observed during the increase in baroreceptor activity helps reduce systemic vasoconstriction and renal retention of water. That is why the regulatory role of arterial baroreceptors in the fluctuations of BP short term and sustained

On the other hand, there is accumulating evidence suggesting that sympathetic nerve activity plays an important role in the pathogenesis of essential hypertension. The findings indicate that sympathetic arousal is especially pronounced in patients who are difficult to control BP as in isolated systolic hypertension, hypertension associated with obesity and

Early studies on the role of the baroreflex in the control of BP, were held in 1950 in dogs to which electrical stimulation of the carotid sinus was applied, showing significant decrease in BP in normotensive and hypertensive animals. (Morrissey, Brookes & Cooke., 1953) These data suggest that the baroreflex is important in chronic hypertension and renal sympathetic inhibition with an increase in natriuresis what could be the mechanism by which the

After overcoming years of many technical difficulties, Tuckman implanted stimulators in both carotid sinuses allowing the regulation of stimulus achieving a BP reduction without adverse effects for a period of 2 to 18 months. (Tuckman et al., 1972) Other researchers conducted studies with similar results. (Parsonnet et al., 1969, Rothfeld et al., 1969, Brest, Wiener & Bachrach., 1972) Currently several studies are underway with a Rheos device that produces chronic electrical stimulation of the carotid sinuses (CVRx, MN, USA): European

Rheos system includes a small pulse generator that is implanted under the collarbone, two thin wires that are implanted in the left and right carotid arteries and are connected to the pulse generator and Rheos programmer system: an external device used by physicians for non-invasive control of the energy delivered by the generator to the overhead wires. In the Device Based Therapy of Hypertension study (Debut-HT), 16 patients completed 2 years of

plasma renin activity and in the renal function. (Voskuil et al.,2011)

elevations in BP are well established. (Guyton et al., 1972)

baroreflex is involved in controlling long term BP.

and U.S. study Feasibility and Rheos Pivotal trial. (Fig.2)

obstructive sleep apnea and in those with a non-dipper of BP pattern.

a longer follow up term.

**14. Baroreflex activation** 

follow up. Both systolic and diastolic BP decreased significantly with 35 ± 8 mmHg and 24 ± 6 mmHg, respectively. In 75% of patients, a decrease in BP of 20 mmHg in systolic BP was shown and 31% achieved BP control. (Scheffers et al., 2008)

In the European and North American study, Rheos system was applied to 16 patients with resistant hypertension which demonstrated a statistically significant decrease in BP in 3 months, along with reduction of left ventricular mass index (-24.1 ± 18.7 g/m2), of the thickness of the septum (- 1.3 ± 1.8 mm), and of the thickness of the left ventricular posterior wall (-1.4 ± 1.1 mm). These results are also accompanied by reduction in the number of antihypertensive drugs used per patient. (de Leeuw et al., 2008) Another study of 12 patients with Rheos system in patients with resistant hypertension showed no deterioration of renal function after 1 year follow up. (Scheffers, Kroon & de Leeuw., 2008) In another 12 patients with resistant hypertension studied by Heusser, showed that electrical stimulation of the baroreceptors decreased systolic BP in 32 ± 10 mmHg, and this one correlated with a reduction in the muscle sympathetic nerve activity, the heart rate and the concentration of plasma renin. (Heusser et al., 2010)

Fig. 2. Rheos System. From CVRx, Rheos, Baroreflex Hypertension Therapy are trademarks of CVRx, Inc. © CVRx, Inc. 2009

At the present time the company CVRx, Inc., the proprietress of this system has announced the introduction of a second generation with an implantable device: The Barostim neo™, with the characteristic to have a smaller generator and a 1 mm unilateral electrode, which should be utilized in resistant hypertension and the HF. (Hasenfuss, 2011)

Without misgivings another investigating step to explain details of efficacy to brief, middle and long term of these devices, their possible interactions with other drugs or surgical procedures, their medical indications, etc., what will permit in the future its use on a wider scale in the resistant hypertension.
