2--hydroxy-5-9-dimethyl-2-allyl-6-7-benzomorphan and Hypertension

Exposure to stress plays a detrimental role in the pathogenesis of hypertension via neuroinflammation pathways. Microglial neuroinflammation in the rostral ventrolateral medulla (RVLM) exacerbates stress-induced hypertension (SIH) by increasing sympathetic hyperactivity. Mitochondria of microglia are the regulators of innate immune response. Sigma-1R (σ-1R) localizes to the mitochondria-associated membranes (MAMs) and regulates endoplasmic reticulum (ER) and mitochondria communication, in part through its chaperone activity. The present study aims to investigate the protective role of σ-1R on microglial-mediated neuroinflammation. Stress-induced hypertension (SIH) was induced in rats using electric foot shocks and intermittent noise. Arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured to evaluate the sympathetic nervous system (SNS) activities. SKF10047 (100 µM), an agonist of σ-1R, was administrated to rats, then σ-1R localization and MAM alterations were detected by immuno-electron microscopy. Mitochondrial calcium homeostasis was examined in primary microglia and/or BV-2 microglia cells. The effect of SKF10047 treatment on the mitochondrial respiratory function of cultured microglia was measured using a Seahorse Extracellular Flux Analyzer. Confocal microscopic images were performed to indicate mitochondrial dynamics. Stress reduces σ-1R's localization at the MAMs, leading to decreased ER-mitochondria contact and IP3R-GRP75-VDAC calcium transport complexes expression in the RVLM of rats. SKF10047 promotes the length and coverage of MAMs in the prorenin-treated microglia. Prorenin treatment increases mitoROS levels, and inhibits Ca

Topics: Animals; Blood Pressure; Calcium; Cell Polarity; Electroshock; Endoplasmic Reticulum; Heart Rate; Hypertension; Microglia; Mitochondria; Phenazocine; Rats; Receptors, sigma; Sigma-1 Receptor; Sympathetic Nervous System