Hypercholesterolemia blunts the oxidative stress elicited by hypertension in venules through angiotensin II type-2 receptors

Abstract

OBJECTIVE Hypertension and hypercholesterolemia elicit inflammatory and thrombogenic responses in the microvasculature. However, little is known about whether and how risk factor combinations alter microvascular function. We examined how the actions of HTN+HCh on the microvasculature differ from the responses elicited by either risk factor alone. METHODS Intravital microscopy was used to monitor the adhesion and emigration of leukocytes and dihydrorhodamine oxidation in cremaster muscle venules of wild type mice that were infused with angiotensin II for 2 wks (HTN), placed on a high cholesterol diet (HCD), or both. RESULTS Either HTN or HCh alone enhanced the production of reactive oxygen species and promoted the recruitment of leukocytes in venules. However, the combination of HTN and HCh produced changes in ROS production and leukocyte recruitment that were greatly attenuated compared to HTN alone. The inhibitory effects of HCh on the AngII mediated responses were also observed in genetically-induced HCh (ApoE-deficient mice). Treating HCh + HTN mice with an antagonist to AT2r reversed the HCh-dependent protection against oxidative stress and inflammation during HTN. CONCLUSIONS These findings indicate that HCh blunts the oxidative stress and inflammatory cell recruitment elicited by hypertension in venules through a mechanism that involves AT2 receptor activation.

Hypertension and the Brain: A Risk Factor for More Than Heart Disease

“…Despite existing evidence linking endothelial activation and cSVD, the fact that elevated circulating markers of endothelial activation in patients with cSVD may derive from any vascular bed permits direct association of cerebro-endothelial activation, inflammation-induced artery stiffening and resulting impairment of auto-regulation of CBF. Nevertheless, there is evidence showing elevation of adhesion molecules, leukocyte rolling along cerebral vessels and T-cells infiltration and accumulation in perivascular spaces during hypertension that suggest a causative link between endothelial activation and cerebrovascular dysfunction [78][79][80] .…”

Rice Germosprout Extract Protects Erythrocytes from Hemolysis and the Aorta, Brain, Heart, and Liver Tissues from Oxidative Stress In Vitro

“…For example, oxidative stress contributing to lipid peroxidation is one of the critical factors involved in the genesis and the progression of nonalcoholic steatohepatitis and liver cancer [ 44 , 45 ]. Besides, oxidative stress is increasingly being recognized as a fundamental factor in the pathologic changes observed in various vascular diseases including hypertension and hypercholesterolemia [ 3 ]. Thus, inhibition of oxidative stress (indicated by reduced levels of LPO) in the aorta, heart, and liver tissues by germosprout extract suggests that it has considerable influence on various oxidative stress-instigated pathologic changes in the liver and the cardiovascular system.…”

“…Oxidative stress is essentially an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by its own antioxidants [ 1 , 2 ]. Oxidative stress has been reported as the contributing factor in various diseases such as inflammatory diseases, ischemic heart diseases, hypertension, hypercholesterolemia, stroke, various liver diseases, hemochromatosis, neurodegenerative disorders, and smoking-related diseases [ 3 – 8 ] and in the impairment of erythrocyte functions including hemolysis [ 9 ]. An excess of oxidative stress can lead to the oxidation of lipids and proteins, which is associated with changes in their structures and functions.…”

Correcting the imbalanced protective RAS in COVID-19 with angiotensin AT2-receptor agonists

“…There is a host of data indicating powerful anti-inflammatory actions of AT 2 R within the parenchymal tissues of multiple organ systems throughout the body [73,75]. This includes the lungs [26,82,83,97], heart [85,92,98,99], kidney [100][101][102][103], vasculature [72,73,102,[104][105][106][107][108] and the central nervous system (CNS) [109][110][111][112][113][114][115][116]. These anti-inflammatory actions of AT 2 R activation at non-immune tissues and cells largely involve interruption of intracellular signalling pathways that lead to production of pro-inflammatory cytokines, and also through induction of pathways that elicit production of anti-inflammatory cytokines such as IL-10 [73,75,116].…”