62 rabbits an increase in blood pressure (as well as in cardiac output and heart rate) after bilateral transection of the carotid nerves. Later on, several other investigators noted that blood pressure became very unstable after denervation of the baroreceptors. Taken together, their data suggested that the primary function of the baroreceptor system is to stabilize blood pressure and to prevent large, short-term pressure fluctuations. Accordingly, Cowley, Liard, and Guyton [4] proposed that the baroreflex system is not important for the long-term regulation of blood pressure and that previous data on the development of hypertension after carotid sinus nerve denervation in animals had been highly exaggerated, presumably as a result of methodologic errors. Nonetheless, interest in the role of the baroreceptor system in hypertension has continued, and various methods have been developed to challenge the system. These methods include blocking the carotid sinus area using procaine or lidocaine and stimulating it using epinephrine. Other researchers have stimulated the carotid sinus area using the neck cuff technique. With this device, it is possible to create a negative pressure around the neck, resulting in increased transmural pressure in the carotid arteries. Such stimulation of the baroreceptor elicits significant decreases in blood pressure, heart rate, and cardiac output in both hypertensive and normotensive subjects. Kubicek and colleagues [5] wondered why the barore- ceptor system fails to restore blood pressure to normal levels in hypertensive patients. Using chronic splanchnic nerve stimulation, they discovered the mechanism of resetting of the baroreceptor system. Their data indicated that it is possible for the baroreceptors and/or the central nervous system pathways to adapt to chronically elevated arterial blood pressure. Subsequently, electroneurographic studies showed fewer impulses along the carotid sinus nerve in dogs with renal hypertension than in normotensive dogs [6]. These results implied that once the reflex was reset, the baroreceptor system would act to maintain the blood pressure at the elevated level. Bristow and colleagues [7] showed that the baroreceptor system in patients with hypertension not only is reset, but also is less sensitive. They assessed baroreceptor sensitivity based on the relationship between changes in systolic blood pressure and changes in R-R intervals after intravenous bolus injections of angiotensin II. Subsequently, several research groups confirmed that the baroreceptor system is less sensitive under conditions of elevated pressure. Angell- James and George [8] concluded that, at least in rabbits, the reduction in baroreceptor sensitivity is related more closely to the duration of hypertension than to its severity. All these data support the notion that the baroreflex system more or less passively follows the development of hypertension and Curr Hypertens Rep (2010) 12:61–66 that activation of the system is unlikely to produce sustained reductions in blood pressure. Early Experiments on Carotid Baroreflex Activation Animal Experiments Despite the foregoing, there has been ongoing interest in devices to stimulate the baroreceptor system. Pioneering work was done by Bilgutay and Lillehei [9], who designed a compact, implantable device with two flat, discoid, stainless steel electrodes that were attached directly to the baroreceptor area and sutured in the wall of the carotid arteries. The unit was triggered intermittently by R waves picked up from the heart by an electrode. These inves- tigators reported on the results of their experiments in four groups of dogs: normotensive, acute neurogenic hyperten- sive, renal hypertensive, and arteriosclerotic. Bilateral electrical stimulation of the baroreceptor for 2 h caused a drop in blood pressure in all dogs, but the best results were seen in the hypertensive dogs, with decreases ranging from 28 to 100 mm Hg systolic and from 12 to 75 mm Hg diastolic. Griffith and Schwartz [10] also designed an implantable device with a bipolar electrode that was attached directly to the carotid sinus nerve. They showed that unilateral electrical stimulation in normotensive and renal hypertensive dogs (with or without sectioning of the contralateral carotid sinus nerve) reduced blood pressure in all animals. After the stimulation was discontinued, blood pressure quickly returned to baseline levels. A few years later, Neistadt and Schwartz [11] reported similar results in 14 adult dogs with experimentally induced hypertension. They applied an implantable carotid sinus nerve stimulator with two electrodes and an external rechargeable trans- mitter. On the day of implantation, a 36% decrease of mean arterial pressure was measured. During the first month, three dogs died and five extracted their stimulator, so only six dogs were evaluated at 1 month. The average decrease in mean arterial pressure with carotid nerve stimulation was 30%. After 2 months, three dogs could be evaluated; at that time, the average decrease in pressure was 23%. In 1969, Agishi and colleagues [12] reported on their experiments with carotid sinus nerve stimulation in mongrel dogs. Direct stimulation caused a drop in blood pressure in all normotensive and hypertensive dogs. Chronic stimula- tion was applied in eight hypertensive dogs and all responded well. Other researchers have also shown a reduction in blood pressure in animals subjected to carotid sinus nerve stimulation. From these experiments, one can conclude that stimulation of the carotid baroreceptor or carotid sinus nerve can, indeed, lower blood pressure, at least in experimental animals.