Sympathoinhibition in Aldosteronism (page 1223)
Recent technology for chronic electric activation of the carotid baroreflex and percutaneous catheter-based renal nerve ablation provides global- and renal-specific suppression of sympathetic activity, respectively, and is currently under investigation for the treatment of resistant hypertension. These nonpharmacological approaches for hypertension therapy have favorable antihypertensive effects in some but not in all patients, and the conditions and mechanisms that account for the variability in blood pressure lowering are unclear. An appreciable number of patients with resistant hypertension have inappropriately high levels of aldosterone, and many of these subjects are not treated with aldosterone antagonists. Accordingly, a study published in this issue of Hypertension evaluated the blood pressure lowering effects of baroreflex activation and bilateral surgical renal denervation in dogs made hypertensive by chronic infusion of aldosterone. When compared with control conditions, the fall in arterial pressure in response to the same intensity of baroreflex activation was diminished ≈55% during aldosterone hypertension. In comparison, renal denervation was completely devoid of antihypertensive effects. These findings are consistent with previous reports indicating that blood pressure lowering during baroreflex activation is not exclusively dependent on neurogenic mechanisms that target the renal nerves. Moreover, these findings in aldosterone hypertension suggest that there may be diminished antihypertensive responses to baroreflex activation and especially renal denervation in the more complex disorder of resistant hypertension in patients not treated with aldosterone antagonists.
Regulatory T Cells and Intrauterine Growth Retardation (page 1298)
Intrauterine growth retardation (IUGR) is a devastating complication of fetal development featuring delayed central nervous system development that is commonly caused by malnutrition and placental insufficiency. IUGR is common in preeclamptic pregnancies. Preeclampsia involves angiogenesis inhibitors, autoantibodies, and cellular immune mechanisms. We used a well-defined transgenic rat model for preeclampsia to investigate the placental-brain axis in IUGR offspring. We focused on T-regulatory lymphocytes (Tregs), specific T cells that serve an immune modulatory function. Tregs are necessary for implantation in the early phase of pregnancy. We showed that upregulating Tregs during preeclampsia ameliorated IUGR, even though they had no effect on the preeclampsia. When we analyzed the fetal brains, we found a 20% increase in brain volume with higher cell density in various brain regions. Immunohistochemical analysis showed an increase in mature neurons and reduced reactive astrogliosis in the fetal cortex after Treg induction early during placentation.
Our data give new insights on how an intervention into the fetal–maternal immune cross talk during placentation can improve IUGR and fetal brain development. They underscore a role for the immune system, not only in the induction of preeclampsia but also in the fetal development. The precise mechanisms of the Treg effects remain unclear. However, earlier research has shown that Tregs control autoantibody-induced inflammation and antibody production, which was reduced in our model after Treg induction. Future research in this field, linking IUGR, fetal–maternal immune cross talk during placentation, and brain development, is urgently needed. Neurobehavioral and cognitive impairments associated with brain immaturity occur in IUGR babies even in the absence of significant brain lesions and have been related to more subtle alterations in brain development.
Dysbiosis in Hypertension (page 1331)
Despite recent advances in pharmacotherapy and lifestyle changes, prevalence of hypertension remains high. Recently, significant focus has centered around the contribution of gut microbiota on metabolic and inflammatory diseases and brain disorders. However, little is known about the role of gut microbiota in hypertension, which exhibits metabolic, inflammatory, and neural components. In the current issue of Hypertension, Yang et al report how gut dysbiosis seems to be critically involved in hypertension using animal models and human fecal samples. Importantly, reshaping a deteriorated gut microbiota using minocycline, a small molecule, anti-inflammatory antibiotic that penetrates the central nervous system, rebalances the gut bacterial community. Resulting growth of beneficial bacteria-producing byproducts (eg, acetate and butyrate) potentially mitigates hypertensive processes in animal models. The outcome of these studies may have significant relevance for clinical intervention. These data may also enlighten critical mechanisms involved in the relationship between hypertension and gut microbiota that govern physiological homeostasis to prevent exacerbated inflammation that may ultimately elicit hypertension. Additional studies should consider focusing on gut microbiota and its metabolomics and metagenomics to draw correlative conclusions for elucidating unique signals involved in steady state and disease status. The overarching goal of these studies is to engender novel concepts and methods by implementing probiotic strategies for the management and treatment of hypertension.
- © 2015 American Heart Association, Inc.