Baroreflex Activation Therapy (page 187)
Despite the availability of many antihypertensive drugs, there are still many hypertensive patients who do not respond adequately to medical treatment. In these patients, device-based baroreflex activation therapy is an attractive option. To date, studies which evaluated the clinical efficacy of baroreflex activation therapy have used bilateral implantation of electrodes. Meanwhile, a new device has become available which allows for unilateral implantation. However, before such a device can be applied on a larger scale, it is necessary to assess whether unilateral stimulation is effective at all. In the present study, unilateral stimulation has been compared with bilateral stimulation in patients who had a bilateral implant. It turns out that unilateral stimulation is even slightly more effective than bilateral stimulation and stimulation on the right side is more effective than stimulation on the left side. This finding has important clinical implications. Restricting the implantation to one side only will reduce operating time and thus reduce hospital and device costs. In addition, it will be beneficial in terms of healing and patient comfort. Although in most patients the right carotid area seems to be dominant in terms of baroreceptor function, there are patients in whom the left side is dominant. Therefore, a challenging area of research will be whether we can predict with noninvasive tests where we should implant the stimulation electrodes.
Hypertension Promotes Alzheimer-Like Pathology (page 218)
The sporadic late onset of Alzheimer disease (AD) is the most frequent form of the disease, usually beginning after 70 or 80 years of age. Once diagnosed, there are few therapeutic options for treating AD; actually, targeting monoclonal antibodies against β-amyloid and Aβ-converting enzyme inhibitors did not succeed. In the absence of effective treatment, it is crucial to focus on AD prevention aiming to reduce the prevalence of AD. Arterial hypertension is undoubtedly one of the main risk factors of AD; epidemiological studies evidenced that reducing the level of blood pressure limits the risk of the onset and slows the progression of AD.
Clinical studies in the field of neurodegenerative diseases are long (10–15 years), technically difficult, and expensive. One of the main advantages of experimental models is to provide reasonable answers, including mechanistic insights, in much shorter periods; mice models of AD develop clinical and histological signs of the disease in ≈8 months.
AD-like mice in the early stages of the disease, before any clinical or biological signs are present, received hypertensive doses of angiotensin II for 10 weeks. In contrast with normotensive transgenic control mice, they evidenced significant cognitive decline and β-amyloid brain deposits.
These experimental data also suggest that, in young preclinical AD-like mice, brain hypoxia resulted in increased angiogenesis. Chronic arterial hypertension reduced brain angiogenesis and impaired the correction of local hypoxia, thus accelerating the onset of signs of AD. These results emphasize the key role of hypertension in the onset of AD and suggest that effective and early treatment of hypertension could reduce the incidence and the severity of the disease. Furthermore, new mechanistic insights could open new therapeutic opportunities.
NO3–NO2–NO Pathway in Hypertension (page 161)
Preglomerular vascular resistance is important for blood pressure control, and emerging evidence emphasizes oxidative stress and nitric oxide (NO) deficiency in development, maintenance, and progression of hypertension. Dietary intervention studies (eg, Dietary Approaches to Stop Hypertension [DASH]-trial) have demonstrated the blood pressure–lowering effects of vegetables, some of which are rich sources of inorganic nitrate. Experimental and clinical studies have shown that dietary supplementation with nitrate, to boost a nitrate–nitrite–NO pathway, can lower blood pressure. However, the target organ and the mechanisms remain largely undetermined. In this issue of Hypertension, Gao et al report that the renal microvasculature is a primary target for the blood pressure–lowering effects of inorganic nitrate and nitrite. In contrast to other vascular beds investigated, renal afferent arterioles were exquisitely responsive to nitrate–nitrite–NO signaling, as demonstrated by vasodilatation and attenuated contractility and blood pressure responses to angiotensin II. Mechanisms involved inhibition of NADPH oxidase and increased NO. These novel findings may explain long-term antihypertensive effects of dietary nitrate and nitrite. Angiotensin II is an essential component of blood pressure regulation and an important modulator of renal autoregulation. Considering previous findings of reno- and cardioprotection with nitrate in models of chronic kidney disease, the interaction between the nitrate–nitrite–NO pathway and angiotensin II–mediated oxidative stress is of particular interest. Future studies will be aimed at translating these findings to patients with hypertension and test the ability of modulating progression of chronic kidney disease.
- © 2014 American Heart Association, Inc.