Sensitization of Hypertension: The Impact of Earlier Life Challenges: Excellence Award for Hypertension Research 2021

Abstract

Hypertension affects over 1 billion individuals worldwide. Because the cause of hypertension is known only in a small fraction of patients, most individuals with high blood pressure are diagnosed as having essential hypertension. Elevated sympathetic nervous system activity has been identified in a large portion of hypertensive patients. However, the root cause for this sympathetic overdrive is unknown. A more complete understanding of the breadth of the functional capabilities of the sympathetic nervous system may lead to new insights into the cause of essential hypertension. By employing a unique experimental paradigm, we have recently discovered that the neural network controlling sympathetic drive is more reactive after rats are exposed to mild challenges (stressors) and that the hypertensive response can be sensitized (ie, hypertensive response sensitization [HTRS]). We have also found that the induction of HTRS involves plasticity in the neural network controlling sympathetic drive. The induction and maintenance of the latent HTRS state also require the functional integrity of the brain renin-angiotensin-aldosterone system and the presence of several central inflammatory factors. In this review, we will discuss the induction and expression of HTRS in adult animals and in the progeny of mothers with prenatal obesity/overnutrition or with maternal gestational hypertension. Also, interventions that reverse the effects of stressor-induced HTRS will be reviewed. Understanding the mechanisms underlying HTRS and identifying the beneficial effects of maternal or offspring early-life interventions that prevent or reverse the sensitized state can provide insights into therapeutic strategies for interrupting the vicious cycle of transgenerational hypertension.

SARS-CoV-2 Spike Protein S1 Exposure Increases Susceptibility to Angiotensin II-Induced Hypertension in Rats by Promoting Central Neuroinflammation and Oxidative Stress

“…First, an initial increase in pressure is associated with an ANGII-mediated systemic vasoconstriction. Then, this phase is replaced by a second, long-term, neurogenic component [ 9 , 24 , 25 ]. In the present studies, the initial increase in BP response to systemic ANG II administration during the first week was comparable between rats pretreated with S1 protein and rats pretreated with VEH.…”

“…It has long been established from both animal and human studies that excessive activation of the sympathetic nervous system plays a primary role in the development and progression of the essential hypertension [ 7 – 9 ]. Inflammation and oxidative stress in the brain, particularly in the hypothalamic paraventricular nucleus (PVN), a cardiovascular regulatory center in the brain that integrates neural and humoral signals driving the sympathetic nervous system, are key factors in regulating sympathetic nerve activity and blood pressure [ 10 , 11 ].…”

“…Inflammation and oxidative stress in the brain, particularly in the hypothalamic paraventricular nucleus (PVN), a cardiovascular regulatory center in the brain that integrates neural and humoral signals driving the sympathetic nervous system, are key factors in regulating sympathetic nerve activity and blood pressure [ 10 , 11 ]. Previous studies have indicated that the presence of several central inflammatory challenges can enhance hypertensive response to subsequent angiotensin (ANG) II administration by promoting inflammation in the brain to increase sympathetic excitation [ 9 , 12 – 14 ]. The S1 subunit of the SARS-CoV-2 spike protein (S1) has been shown to cross the blood–brain barrier (BBB) and cause inflammatory response in the brain independent of SARS-CoV-2 cellular infection [ 15 , 16 ].…”

Recent Advances in Hypertension: Epigenetic Mechanism Involved in Development of Salt-Sensitive Hypertension

“…Using microarrays, hypothalamus-specific genes contributing to the hypertension phenotype were determined, and certain genes that were upregulated >2-fold in developmental origins of health and disease rat models were identified. Pathway analysis revealed that the angiotensin signaling pathway, an important central mechanism regulating sympathetic nerve activity and cardiovascular function, 23 was one of the top-ranked pathways. Consistently, the mRNA expression of angiotensin receptor AT1A in the hypothalamic paraventricular nucleus was significantly higher in low-protein offspring than in normal-protein offspring.…”

Hyperuricemia Increases the Risk of Postoperative Recurrence in Chinese Patients with Chronic Rhinosinusitis

“…Comorbidities were diagnosed as previous publications described. [29][30][31][32] Hypertension was defined as repeated SBP ≥ 140 and/or DBP ≥ 90 mmHg or ongoing anti-hypertensive medications. Diabetes mellitus was diagnosed when FBG ≥ 7.0 mmol/L, 2-h plasma glucose ≥ 11.1 mmol/L, or current consumption of hypoglycemic drugs.…”