Influence of bradykinin B2 receptor and dopamine D2 receptor on the oxidative stress, inflammatory response, and apoptotic process in human endothelial cells

Abstract

Endothelial dysfunction is a hallmark of a wide range of cardiovascular diseases and is often linked to oxidative stress and inflammation. Our earlier study reported the formation of a functional heterodimer between bradykinin receptor 2 (B2R) and dopamine receptor 2 (D2R) that may modulate cell responses, dependent on intracellular signaling. Here, for the first time, we showed a cooperative effect of these receptors on the modulation of processes involved in oxidative stress, inflammation, and apoptosis in endothelial cells. Sumanirole, a specific D2R agonist, was shown to diminish the excessive production of reactive oxygen species induced by bradykinin, a proinflammatory B2R-activating peptide. This effect was accompanied by modified activities of antioxidant enzymes and increased phosphorylation of endothelial nitric oxide synthase, leading to enhance NO production. In turn, endothelial cell co-stimulation with B2R and D2R agonists inhibited the release of interleukin-6 and endothelin-1 and modulated the expression of apoptosis markers, such as Bcl-2, Bcl-xL, Bax, and caspase 3/7 activity. All these observations argue that the D2R agonist counteracts the pro-oxidative, pro-inflammatory, and pro-apoptotic effects induced through B2R, finally markedly improving endothelial functions.

Stimulation of dopamine D2 receptor via quinpirole protects against brain damage after brain injury in mice

“…Our results are consistent with the previous that D2R agonist reduced neuronal cells apoptosis [57]. Further study provides evidence that D2R agonist reduced oxidative stress, neuroinflammation, and apoptosis in endothelial cells [58]. In order to know the dead and damaged neuron and morphology of the brain tissue, we performed the morphological analysis after brain injury.…”

Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors

“…Apoptosis is a common cellular strategy to control virus dissemination, and prolonged cell survival may result in higher viral loads [ 57 , 68 , 69 ]. In vitro studies with endothelial cells have previously linked the B2R activation and NO pathway to modulation of cellular proliferation and apoptosis [ 57 , 70 , 71 ]. Since DENV-2 infection is known to induce HBMECs cell death [ 59 ], we sought to determine whether this anti-viral response was suppressed as due to activation of the B2R/NO pathway.…”

Dopamine receptor D2 inhibition alleviates diabetic hepatic stellate cells fibrosis by regulating the TGF‐β1/Smads and NFκB pathways

“…Previous studies have demonstrated that DRD2 mediates dopamine signalling and inhibits glucose‐stimulated insulin release 12 . DRD2 has also been reported to be important for the maintenance of a normal redox balance and is related to NADPH oxidase activity, especially NOX‐5 15 . NOX‐5 can produce excessive ROS in the liver and play a key role in promoting various liver diseases, including liver fibrosis; 15,16 however, the exact mechanism is unknown.…”

“…DRD2 has also been reported to be important for the maintenance of a normal redox balance and is related to NADPH oxidase activity, especially NOX‐5 15 . NOX‐5 can produce excessive ROS in the liver and play a key role in promoting various liver diseases, including liver fibrosis; 15,16 however, the exact mechanism is unknown. Immunoblotting showed that diabetes increased DRD2 and NOX‐5 expression in vivo, which suggested that diabetes‐induced liver dysfunction is associated with up‐regulation of DRD2 and increased in oxidative stress.…”

“…DRD2 is reported to be involved in regulating the balance between ROS generation and the antioxidant system, and this function is related to the role of DRD2 in regulating nicotinamide adenine dinucleotide phosphate(NADPH) oxidase activity 15 . NADPH oxidase (NOX), especially NOX‐5, which causes excessive production of ROS in the liver, is involved in the progression of various liver diseases, including liver fibrosis 16,17 .…”