NHE3-Inhibition in the Gut and Hypertension (page 1560)
High intestinal sodium absorption is 1 mechanism of hypertension and constipation. The sodium-proton-exchanger subtype 3 (NHE3) is an important mediator of sodium absorption in the gut. SAR218034 is an orally nonabsorbable specific NHE3 inhibitor. Inhibition of intestinal NHE3 by SAR218034 increased feces sodium-excretion and reduced urinary sodium-excretion, while absolute sodium balance and serum sodium-concentration was not changed. Reduced intestinal sodium absorption by SAR218034-treatment was associated with increased feces water content and reduction in systolic blood pressure. Angiotensin-converting enzyme inhibition by ramipril plus NHE3 inhibition resulted in an additive blood pressure lowering effect. Selective inhibition of NHE3-mediated sodium absorption in the gut has the potential to reduce high blood pressure and can be safely combined with angiotensin-converting enzyme inhibitor treatment. In addition, NHE3 inhibition in the gut may display a laxative effect in elderly patients suffering from constipation. These results show that SAR218034 inhibiting intestinal NHE3-mediated sodium absorption has potential as a representative of a new class of antihypertensive drugs. Intestinal NHE3 inhibitors may be particularly useful as an adjunct to other therapies. The real potential of the NHE3 inhibitor is to help accomplish a truly low salt-intake from the gut, because it is difficult to sufficiently reduce salt in the human diet.
Quality of Life After Renal Denervation (page 1479)
Recent studies have demonstrated the effectiveness of radiofrequency ablation of the renal sympathetic nerves in reducing blood pressure in patients with treatment resistant hypertension. In this issue of Hypertension, Lambert et al present data indicating that subjective health-related quality of life, as assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey, is markedly diminished in patients with treatment resistant hypertension. Three months after renal denervation, the 36-Item Short-Form Health Survey mental component summary score improved, with the change being driven by increases in the vitality, social function, role emotion, and mental health domains. No change occurred in the physical component summary score. The changes in 36-Item Short-Form Health Survey scores were not related to the magnitude of blood pressure reduction. Although the authors could not exclude the possibility of a placebo effect, the potential mechanisms underlying their observations are intriguing. Preclinical studies have demonstrated that sensory renal afferent nerves can influence the firing rate of medullary and hypothalamic neurones and that renal afferent denervation prevents the development of hypertension and an increase in norepinephrine turnover in the posterior and lateral hypothalamic nuclei and the locus coeruleus. The majority of brain norepinephrine is located in the locus coeruleus, which, together with its hypothalamic and amygdala projections, is linked with behavioral responses involving autonomic activation. Whether the improvement in health-related quality of life that occurred after renal denervation is sustained and has a biological basis associated with reduction in sympathetic tone remains unknown but does merit further attention.
Blood Pressure Tracking Over the Life Course (page 1393)
Although prior studies have shown that blood pressure steadily increases with age, there are limited longitudinal data characterizing the pattern of blood pressure tracking over the life course. Furthermore, the extent to which risk factors influence blood pressure tracking is not well understood. Therefore, we used multilevel modeling to analyze blood pressure measurements performed serially, over a period of up to 28 years, in participants of the Framingham Heart Study. On the basis of data collected from >21 700 person-observations, we observed that risk factors such as greater body mass index and higher heart rate were associated with an increase in all component measures of blood pressure. However, dyslipidemia was primarily associated with increased mean arterial pressure, a measure of steady-state load, whereas diabetes mellitus and smoking were predominantly associated with higher pulse pressure, representing pulsatile load. Notably, age-related increases in pulse pressure were more pronounced in women compared with men overall. The differential impact of select risk factors on elevation in the individual components of blood pressure underscores distinct regulation of these measures over the life course. Further research is needed to investigate the mechanisms underlying these observations and, in turn, the extent to which targeted interventions may attenuate the typical trajectory of blood pressure progression with aging.
- © 2012 American Heart Association, Inc.