JS-HR-12: BASIC RESEARCH: ELUCIDATION OF “MOSAIC” PATHOGENESIS OF HYPERTENSION

Abstract

Basic research plays critical roles in elucidating the “mosaic” pathogenesis of hypertension and developing its treatment. In the field of brain and autonomic nervous system, Chen et al. demonstrated that mild cold exposure elicits autonomic dysregulation, such as increased sympathetic activity and decreased baroreflex sensitivity, and poor sleep quality, causing blood pressure (BP) elevation in normotensive rats. This finding may have critical implications for the cardiovascular event occurrence with low ambient temperature. Domingos-Souza et al. showed that the ability of baroreflex activation to modulate hemodynamics and induce lasting vascular adaptation is critically dependent on the electrical parameters and duration of carotid sinus stimulation in spontaneously hypertensive rats (SHRs), proposing a rationale for improving baroreflex activation therapy in humans. In the kidney, Kasacka et al. showed that activity of Wnt/β-catenin pathway is increased in SHRs and 2K1C hypertensive rats, while it is inhibited in DOCA-salt rats. Intrarenal renin-angiotensin system (RAS) is involved in BP regulation. In renal damage with an impaired glomerular filtration barrier, liver-derived angiotensinogen filtered through damaged glomeruli regulates intrarenal RAS activity. Matsuyama et al. further showed that the glomerular filtration of liver-derived angiotensinogen depending on glomerular capillary pressure causes circadian rhythm of the intrarenal RAS. Otsuki et al. revealed that TWIST1, a transcription factor regulating mesodermal embryogenesis, transcriptionally upregulates complement 3, which has been demonstrated to activate intrarenal RAS, in the glomerular mesangial cells from SHRs. The RAS in the vascular system also contributes to BP regulation. Soring nexins (SNXs) are cellular sorting proteins and can regulate the expression and function of G protein-coupled receptors (GPCRs). Liu C et al. demonstrated that SNX1 knockout mice exhibit hypertension through vasoconstriction mediated by increased expression of GPCR AT1R within the arteries. Liu X et al. found that sirtuin 6 (SIRT6) expression is downregulated in the aortae of aged rats and showed that SIRT6 knockdown enhances angiotensin II-induced vascular adventitial aging by activating NF-κB pathway in vitro studies. The studies investigating extracellular vesicles (EVs) and gut microbiota have been increased. Ochiai-Homma et al. showed that pendrin in urinary EVs can be a useful biomarker for diagnosis and treatment of primary aldosteronism. Wu et al. demonstrated that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt hypertensive rats. Several reports indicate the potential treatment for hypertension and the associated organ damages: rivaroxaban in cardiac hypertrophy; nebivolol, maximakinin, and Pinggan-Qianyang in hypertension; and melatonin and crocin in gestational hypertension.