Search

Cytokines play a crucial role in the structure and function of blood vessels in hypertension. Hypertension damages blood vessels by mechanisms linked to shear forces, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, oxidative stress, and a proinflammatory milieu that lead to the generation of neoantigens and damage-associated molecular patterns, ultimately triggering the release of numerous cytokines. Damage-associated molecular patterns are recognized by PRRs (pattern recognition receptors) and activate inflammatory mechanisms in endothelial cells, smooth muscle cells, perivascular nerves, and perivascular adipose tissue. Activated vascular cells also release cytokines and express factors that attract macrophages, dendritic cells, and lymphocytes to the blood vessels. Activated and differentiated T cells into Th1, Th17, and Th22 in secondary lymphoid organs migrate to the vessels, releasing specific cytokines that further contribute to vascular dysfunction and remodeling. This chronic inflammation alters the profile of endothelial and smooth muscle cells, making them dysfunctional. Here, we provide an overview of how cytokines contribute to hypertension by impacting the vasculature. Furthermore, we explore clinical perspectives about the modulation of cytokines as a potential therapeutic intervention to specifically target hypertension-linked vascular dysfunction., Competing Interests: Disclosures None.

Cytomegalovirus (CMV) is a member of the β-herpesviruses and is ubiquitous, infecting 50%-99% of the human population depending on ethnic and socioeconomic conditions. CMV establishes lifelong, latent infections in their host. Spontaneous reactivation of CMV is usually asymptomatic, but reactivation events in immunocompromised or immunosuppressed individuals can lead to severe morbidity and mortality. Moreover, herpesvirus infections have been associated with several cardiovascular and post-transplant diseases (stroke, atherosclerosis, post-transplant vasculopathy, and hypertension). Herpesviruses, including CMV, encode viral G-protein-coupled receptors (vGPCRs) that alter the host cell by hijacking signaling pathways that play important roles in the viral life cycle and these cardiovascular diseases. In this brief review, we discuss the pharmacology and signaling properties of these vGPCRs, and their contribution to hypertension. Overall, these vGPCRs can be considered attractive targets moving forward in the development of novel hypertensive therapies., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cardiovascular diseases (CVD) are the number 1 cause of death in the United States and hypertension is a highly prevalent risk factor for CVD. It is estimated that up to 50 % of the hypertensive trait is genetically inherited while the other 50 % is determined by modifiable factors involving lifestyle, behaviors, and the environment. Interestingly, the hypertensive trait is induced or inhibited by epigenetic modifications modulated by modifiable factors. This review focused on the underlying mechanisms of stress, sleep deprivation, obesity and sedentarism as key players for epigenetic modifications contributing to the development of the hypertensive trait and, on the other hand, how epigenetic modifications induced by physical exercise and healthier habits may contribute to overturn and prevent the inheritance of hypertension trait. Furthermore, adversities during gestation and perinatal life also increase the risk for hypertension and CVD later in life, which can perpetuate the inheritance of the hypertensive trait whereas healthier habits during gestation and lactation may counteract fetal programming to improve the cardiovascular health of the progeny. Therefore, it is promising that a healthier lifestyle causes long-lasting epigenetic modifications and is transmitted to the next generation, strengthening the fight against the inheritance of hypertension., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

People living with hypertension have a higher risk of developing heart diseases, and hypertension remains a top cause of mortality. In hypertension, some detrimental changes occur in the arterial wall, which include physiological and biochemical changes. Furthermore, this disease is characterized by turbulent blood flow, increased fluid shear stress, remodeling of the blood vessels, and endothelial dysfunction. As a complex disease, hypertension is thought to be caused by an array of factors, its etiology consisting of both environmental and genetic factors. The Mosaic Theory of hypertension states that many factors, including genetics, environment, adaptive, neural, mechanical, and hormonal perturbations are intertwined, leading to increases in blood pressure. Long-term efforts by several investigators have provided invaluable insight into the physiological mechanisms responsible for the pathogenesis of hypertension, and these include increased activity of the sympathetic nervous system, overactivation of the renin-angiotensin-aldosterone system (RAAS), dysfunction of the vascular endothelium, impaired platelet function, thrombogenesis, vascular smooth muscle and cardiac hypertrophy, and altered angiogenesis. Exosomes are extracellular vesicles released by all cells and carry nucleic acids, proteins, lipids, and metabolites into the extracellular environment. They play a role in intercellular communication and are involved in the pathophysiology of diseases. Since the discovery of exosomes in the 1980s, numerous studies have been carried out to understand the biogenesis, composition, and function of exosomes. In this review, we will discuss the role of exosomes as intercellular messengers in hypertension.

The virus responsible for the coronavirus disease of 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidences suggest that COVID-19 could trigger cardiovascular complications in apparently healthy patients. Coronaviruses are enveloped positive-strand RNA viruses acting as a pathogen-associated molecular pattern (PAMP)/ danger-associated molecular patterns (DAMP). Interestingly, Toll-like receptor (TLR) 3 recognize both PAMPs DAMPs and is activated by viral double-stranded RNA (dsRNA) leading to activation of TIR receptor domain-containing adaptor inducing IFN-β (TRIF) dependent pathway. New evidence has shown a link between virus dsRNA and increased BP. Hence, we hypothesize that COVID-19 infection may be over activating the TLR3 through dsRNA, evoking further damage to the patients, leading to vascular inflammation and increased blood pressure, favoring the development of several cardiovascular complications, including hypertension., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cells respond to stress by activating a variety of defense signaling pathways, including cell survival and cell death pathways. Although cell survival signaling helps the cell to recover from acute insults, cell death or senescence pathways induced by chronic insults can lead to unresolved pathologies. Arterial hypertension results from chronic physiological maladaptation against various stressors represented by abnormal circulating or local neurohormonal factors, mechanical stress, intracellular accumulation of toxic molecules, and dysfunctional organelles. Hypertension and aging share common mechanisms that mediate or prolong chronic cell stress, such as endoplasmic reticulum stress and accumulation of protein aggregates, oxidative stress, metabolic mitochondrial stress, DNA damage, stress-induced senescence, and proinflammatory processes. This review discusses common adaptive signaling mechanisms against these stresses including unfolded protein responses, antioxidant response element signaling, autophagy, mitophagy, and mitochondrial fission/fusion, STING (signaling effector stimulator of interferon genes)-mediated responses, and activation of pattern recognition receptors. The main molecular mechanisms by which the vasculature copes with hypertensive and aging stressors are presented and recent advancements in stress-adaptive signaling mechanisms as well as potential therapeutic targets are discussed.

Morphological and physiological changes in the vasculature have been described in the evolution and maintenance of hypertension. Hypertension-induced vascular dysfunction may present itself as a contributing, or consequential factor, to vascular remodeling caused by chronically elevated systemic arterial blood pressure. Changes in all vessel layers, from the endothelium to the perivascular adipose tissue (PVAT), have been described. This mini-review focuses on the current knowledge of the structure and function of the vessel layers, specifically muscular arteries: intima, media, adventitia, PVAT, and the cell types harbored within each vessel layer. The contributions of each cell type to vessel homeostasis and pathophysiological development of hypertension will be highlighted.

The aim of this work was to evaluate the influence of run training on the responsiveness of corpus cavernosum (CC) from rats made hypertensive by treatment with nitric oxide (NO) synthesis inhibitor. Wistar rats were divided into sedentary control (C-SD), exercise training (C-TR), N(omega)-nitro-L-arginine methyl ester (L-NAME) sedentary (LN-SD) and L-NAME trained (LN-TR) groups. The run training program consisted in 8 weeks in a treadmill, 5 days/week, each session lasted 60 min. L-NAME treatment (2 and 10 mg/rat/day) started after 4 weeks of prior physical conditioning and lasted 4 weeks. Concentration-response curves were obtained for acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil and BAY 41-2272. The effect of electrical field stimulation (EFS) on the relaxations responses of CC was evaluated. Run training prevented the arterial hypertension induced by L-NAME treatment (LN-SD: 135+/-2 and 141+/-2 mm Hg for both doses of L-NAME) compared to LN-SD groups (154+/-1 and 175+/-2 mm Hg, for 2 and 10 mg of L-NAME, respectively). Run training produced an increase in the maximal responses (E(max)) of CC for ACh (C-SD: 47+/-3; C-TR: 52+/-1; and LN-TR: 53+/-3%) and SNP (C-SD: 89+/-1; C-TR: 98+/-1; and LN-TR: 95+/-1%). Both potency and E(max) for ACh were reduced in a dose of 10 mg of L-NAME, and run training restored the reduction of E(max) for ACh. No changes were found for BAY 41-2271 and sildenafil. Relaxing responses to EFS was reduced by L-NAME treatment that was restored by prior physical conditioning. In conclusion, our study shows a beneficial effect of prior physical conditioning on the impaired CC relaxing responses in rats made hypertensive by chronic NO blockade.

Introduction: Childhood obesity is a worrisome health concern for children and teenagers, as it can contribute to several health issues in adulthood, including diabetes, high blood pressure, and high cholesterol. These conditions have been associated with sexual dysfunction. However, the precise impact of early childhood obesity on erectile function in adult males remains uncertain. Objective: We hypothesized that overfeeding during early childhood can have lasting effects on body fat distribution, blood pressure, and erectile function in young adult males. Methods: On postnatal day (PND 1), Wistar rats were separated into two groups: normal litter (NL) with 10 pups per dam, or small litter (SL) with 3 pups per dam. Male rats (n = 8-10 per group) were then assessed at two different time points: during the prepubertal stage (PND 40) and in adulthood (PND 120). Erectile function was assessed only after sexual maturation (i.e., on PND 120). Body weight, retroperitoneal and perigonadal adipose tissue (fat pad weight/100g of the body) were evaluated. The mean blood pressure (MBP) was recorded in conscious rats using the indirect tail-cuff method. Following euthanasia at PND 120, the corpus cavernosum was removed to perform functional studies using a strip myograph. Contractile and relaxation responses were evaluated by electrical field stimulation (EFS) and concentration-response curves (CRC) to phenylephrine [Phe, 1nM-30μM, millinewton (mN)] or acetylcholine (Ach 1nM-30μM, % relaxation) were performed. Results: At the prepubertal stage, SL rats had higher body weight (NL 149±3 vs. SL 186±5, g, p<0.05), and increased retroperitoneal (NL 0.17±0.01 vs. SL 0.32±0.03, g, p<0.05) and perigonadal (NL 0.38± 0.02 vs. SL 0.45±0.03, g, p<0.05) adipose tissue. At PND 120, SL group presented increased body weight (NL 534±13vs. SL 631.6±10, g/100g, p<0.05), retroperitoneal (NL 1.31±0.11vs. SL 1.82±0.14, g/100g, p<0.05) and perigonadal (NL1.74±0.10vs. SL 2.18±0.15, g/100g, p<0.05) adipose tissue when compared with NL group. Moreover, SL rats presented increased MBP (NL 114.9±0.58 vs SL 120.5±1.2, mmHg). The corpus cavernosum of SL rats at PND 120 had increased contraction induced by EFS for all frequencies (1 Hz: NL 0.5 ± 0.2 mN vs SL 0.9 ± 0.2 mN; 4 Hz: NL 1.2 ± 0.3 mN vs SL 1.8 ± 0.2 mN; 16 Hz: NL 1.9 ± 0.4 mN vs SL 3 ± 0.4 mN), whereas the relaxation was decreased (1 Hz: NL 0.77 ± 0.18% vs SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs SL 2.39 ± 0.53%). CRC showed increased contractile response to Phe (Emax NL 2.3±0.3 vs. SL 3.8± 0.6, mN, p=0.05) and reduced potency of ACh (pEC50 NL 6.4±0.6 vs SL 4.9±0.7, mN, p=0.1) in the corpus cavernosum of SL. Incubation with indomethacin (10uM) abolished the differences in the contractile response induced by EFS or Phe between SL and NL, suggesting a heightened inflammatory response. Conclusions: These data suggest that early childhood obesity has long-lasting negative implications on sexual function in adulthood. Disclosure: No. [ABSTRACT FROM AUTHOR]