Central EP3 (E Prostanoid 3) Receptors Mediate Salt-Sensitive Hypertension and Immune Activation
Year: 2019
Type: article
Abstract: We recently identified a pathway underlying immune activation in hypertension. Proteins oxidatively modified by reactive isoLG (isolevuglandin) accumulate in dendritic cells (DCs). PGE 2 (Prostaglandin E2) has been implicated in the inflammation associated with hypertension. We hypothesized that PGE 2 via its EP (E prostanoid) 3 receptor contributes to DC activation in hypertension. EP3 −/− mice and wild-type littermates were exposed to sequential hypertensive stimuli involving an initial 2-week exposure to the nitric oxide synthase inhibitor N ω -nitro-L-arginine methyl ester hydrochloride in drinking water, followed by a 2-week washout period, and a subsequent 4% high-salt diet for 3 weeks. In wild-type mice, this protocol increased systolic pressure from 123±2 to 148±8 mm Hg ( P <0.05). This was associated with marked renal inflammation and a striking accumulation of isoLG adducts in splenic DCs. However, the increases in blood pressure, renal T-cell infiltration, and DC isoLG formation were completely prevented in EP3 −/− mice. Similar protective effects were also observed in wild-type mice that received intracerebroventricular injection of a lentiviral vector encoding shRNA targeting the EP3 receptor. Further, in vitro experiments indicated that PGE 2 also acts directly on DCs via its EP1 receptors to stimulate intracellular isoLG formation. Together, these findings provide new insight into how EP receptors in both the central nervous system and peripherally on DCs promote inflammation in salt-induced hypertension.
Source: Hypertension
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: green
Awards: Targeting Mitochondrial Cyclophilin D in Vascular Oxidative Stress and Hypertension, Mechanisms of Immune Activation in Hypertension, PGE2 signaling in Hypertension: The role of EP receptors in the immune system, Sirtuin 3 Inactivation and SOD2 Acetylation in Vascular Dysfunction and Hypertension, G5896623678, G7126395394, G7176007276, PPARG-dependent Mechanisms Control Endothelial-Smooth Muscle Coordination, Arterial Pressure, Vasomotor Function and Arterial Stiffness, Angiotensin receptor G protein signal switching in AgRP neurons in cardiometabolic control
OpenAlex ID: W2983534058