Skip to main content
. 2022 Feb 9;128(6):915–930. doi: 10.1016/j.bja.2022.01.012

Fig 4.

Fig 4

Interplay between renin-angiotensin-aldosterone system, inflammation and endothelial dysfunction. Angiotensin II, a pivotal mediator of developing higher blood pressure, directly activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which directly generates reactive oxygen species (ROS). Additional ROS release induced by damaged mitochondria, plus uncoupled nitric oxide synthase and xanthine oxidase, also contributes to injury in multiple cell types, including endothelial, vascular smooth muscle, neuronal, and renal tubular cells. Upregulation of pro-inflammatory TLR4 receptors, which detect pathogen and danger-associated molecules predispose individuals with higher blood pressure to an exaggerated innate immune response. CD14, cluster of differentiation 14; ERK, extracellular signal-regulated kinases; ICAM, intercellular adhesion molecule 1; iκB, inhibitor of κb; IL23, interleukin 23; JNK, c-Jun N-terminal kinases; MD-2, myeloid differentiation factor 2; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; ONOO–, peroxynitrite; p38 MAPK, p38 mitogen-activated protein kinase; TLR4, Toll-like 4 receptor; TNFα, tumour necrosis factor alpha; VCAM, vascular cell adhesion molecule 1.