Ethanol-Induced White Matter Atrophy Is Associated with Impaired Expression of Aspartyl-Asparaginyl-β-Hydroxylase (ASPH) and Notch Signaling in an Experimental Rat Model.

Hypertension, or high blood pressure (BP), is a widespread condition affecting one in three adults globally. Despite the availability of treatment options, 50% of hypertensive patients in countries such as Australia fail to achieve adequate BP control, often due to a lack of response to current therapies. Diet plays a crucial role in BP regulation. A high-fibre diet reduces BP through the gut microbiome and the production of microbial metabolites known as short-chain fatty acids (SCFAs). However, the mechanisms of BP regulation by SCFAs remained still unclear. A novel hypothesis we explore in this review is that these microbial metabolites may regulate BP via the activation of central mechanisms, a phenomenon called the gut-brain axis. While substantial evidence in animal models and humans supports the protective role of SCFAs in hypertension, the precise mechanisms remain unclear. SCFA stimulates the release of neurotransmitters and hormones such as serotonin, cholecystokinin, glucagon-like peptide 1 and peptide YY by enteroendocrine cells, a rare population of cells lining the gastrointestinal tract. These hormones bind to their receptors on the peripheral nervous system nerves, such as the vagus and spinal nerves, conveying information to the brain. The mechanisms by which information is relayed from the gut microbiome to the brain likely involve the immune system and gut-derived neurotransmitters and hormones. A deeper understanding of these pathways and mechanisms will facilitate the development of novel therapeutics for hypertension and other cardiovascular diseases.