The colonic epithelium is the site of production and transport of many vasoactive metabolites and neurotransmitters that can modulate the immune system, affect cellular metabolism, and subsequently regulate blood pressure. As an important interface between the microbiome and its host, the colon can contribute to the development of hypertension. In this critical review, we highlight the role of colonic inflammation and microbial metabolites on the gut brain axis in the pathology of hypertension, with special emphasis on the interaction between tumor necrosis factor α (TNFα) and short chain fatty acid (SCFA) metabolites. Here, we review the current literature and identify novel pathways in the colonic epithelium related to hypertension. A network analysis on transcriptome data previously generated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats reveals differences in several pathways associated with inflammation involving TNFα (NF-κB and STAT Expression Targets) as well as oxidative stress. We also identify down-regulation of networks associated with gastrointestinal function, cardiovascular function, enteric nervous system function, and cholinergic and adrenergic transmission. The analysis also uncovered transcriptome responses related to glycolysis, butyrate oxidation, and mitochondrial function, in addition to gut neuropeptides that serve as modulators of blood pressure and metabolic function. We present a model for the role of TNFα in regulating bacterial metabolite transport and neuropeptide signaling in the gastrointestinal system, highlighting the complexity of host–microbiota interactions in hypertension.

Tumor Necrosis Factor Alpha and the Gastrointestinal Epithelium: Implications for the Gut-Brain Axis and Hypertension.

Disrupted regulation of ghrelin production under antihypertensive treatment in spontaneously hypertensive rats

Objectives The diffuse neuroendocrine system (DNES) participates in the systemic homeostasis and may work as a unified system with integrated functions but anatomically disperse. However, the mechanisms that are involved in the integration of the distant parts of the DNES are poorly known. This study is aimed on the effects of a pinealectomy on the population of the neuroendocrine cells (NECs) in the colon of rats. Methods A group of seven newborn rats and one of adult rats were submitted to a pinealectomy. The animals were sacrificed after 15 days and 90 days, respectively. The control groups of adult and newborn rats were subjected to a 'sham surgery' and then sacrificed after similar periods of time. Paraffin-included sections of the colon samples were stained by the Churukian-Schenk method in order to selectively stain the NECs. The NEC index was estimated by the expression: iNEC = NECs population per crypt/Total cell population of the crypt. The results were expressed as median and absolute range, and the statistical significance was demonstrated by the Mann-Whitney (U) test. Results The morphometric analysis showed a significant increase in the number of colonic NECs of the adult rats subjected to a pinealectomy when compared to the controls. No statistical difference was observed between the iNECs of the newborn groups of rats. Conclusion This finding suggests the existence of regulatory mechanisms that integrate distant parts of the DNES, by adapting the population of the endocrine cells after the ablation of an important component of the system. Further studies on the mechanisms involved in the integration of the DNES may be facilitated by the simple experimental model that we propose.

Hyperplasia of the colonic neuroendocrine cells after pinealectomy in rats. The new evidence for the existence of connections between the distant parts of the diffuse neuroendocrine system.

Simple Summary The endocrine cells of the alimentary tract (APUD) are an important component of the mucosa structure and significantly influence the stomach and intestine physiology. Prenatal development of the stomach is not limited to the qualitative and quantitative changes observed in the gastric wall, but is also reflected in APUD cell occurrence and their potential function in the development and maturation of the organ. Moreover, the perinatal period, crucial for the colostral globulin intake by the new-born animal, requires an adequately prepared gastric mucosa and its excretory function must be controlled. This study was aimed at immunohistochemical changes observed in the foetal period in equine foetuses. The changes were related to the reactivity of the endocrine cells and allowed us to better understand the developmental processes taking place both in the prenatal and perinatal period. Abstract The study consisted of the immunohistochemical analysis of fundic and pyloric mucosa in the equine stomach between the 4th and 11th month of gestation. The accessible material was classified into three age groups using the CRL method. The adult reference group was used to define potential differences between foetal and adult populations of gastric APUD cells. The samples were preserved, prepared, and stained according to the standard protocols. The immunohistochemical reaction was assessed using the semi-quantitative IRS method. The results were documented and statistically analysed. The most significant increase was seen in gastrin (G) cell activity. The activity of other endocrine cells (cholecystokinin (I) cells, somatostatin (D) cells, and somatotropin receptor (SR) cells) was less dynamic. This study proved that the development of APUD cells within the stomach mucosa undergoes quantitative and qualitative changes during stomach development. Our results correspond with the findings described in the accessible literature and prove a strong correlation between morphological changes in the stomach wall and the organ development, growth, and maturation.

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Equine Stomach Development in the Foetal Period of Prenatal Life—An Immunohistochemical Study

The Role of the Neuroimmune Network in Allergic Inflammation

____________________________________________________________________________________________________ Recent years have witnessed a progressive increase in the number of people suffering from hypertension, which is one of the most serious health problems in the world. Hypertension results in changes leading to function disorders, not only of the organs and tissues, but also changes leading to the activation of many defense mechanisms in the cells in order to prevent damage. One of them is the expression of neuroendocrine (NE) hormones and biologically active substances, which has been the focus of extensive research for a number of years. Active involvement of NE cells and the biological and therapeutic properties of various substances synthesized by them have been confirmed in clinical trials and in various experimental models. Results obtained in many research studies indicate intense activity of enteroendocrine cells in the gastrointestinal tract in various pathological conditions, including hypertension. In the present review, we discuss the morphological and functional changes of gastrointestinal neuroendocrine cells under conditions of different types of hypertension.

I. Kasacka

Papers

Gastrointestinal neuroendocrine cells in various types of hypertension –a review