The effect of purinergic signaling via the P2Y11 receptor on vascular function in a rat model of acute inflammation

Abstract

There is a growing body of evidence pointing to the role of purinergic signaling in the development and progression of various conditions that have inflammation as a common pathogenetic denominator. The aim of the present study was to assess the involvement of PY purinergic receptors in the regulation of vascular function in aortic segments obtained using an experimental model of acute inflammation, the lipopolysaccharide (LPS, 8 mg/kg, i.p)-treated rats. Twelve hours after LPS administration, thoracic aortas were isolated and used for studies of vascular reactivity in the organ bath and for the measurement of reactive oxygen species (ROS) generation, respectively. LPS treatment significantly increased contractility to phenylephrine and attenuated the endothelium-dependent relaxation of the vascular segments in response to acetylcholine; an increased production of hydrogen peroxide (HO) was also recorded. The PY activator, NF decreased the LPS-induced aortic HO release and partially normalized the vasomotor function, namely reduced contractility and improved relaxation. The effect was abolished by co-treatment with the PY inhibitor, NF and also after endothelium denudation. Importantly, NF did not elicit an antioxidant effect by acting as a HO scavenger, suggesting that the beneficial outcome of this treatment on the vasculature is the consequence of PY stimulation. In conclusion, purinergic PY receptors stimulation improves vascular function and mitigates oxidative stress in the setting of acute systemic inflammation, revealing salutary effects and therapeutic potential in pathologies associated with endothelial dysfunction.

RETRACTED: Mechanisms Contributing to the Generation of Mayer Waves

“…Interspecies variability of vascular smooth muscle cell contraction and relaxation kinetics may contribute to generating differences in time delay across the baroreflex loop, Mayer wave central frequency ( Seydnejad and Kitney, 2001 ), and frequency of oscillations of arteriolar diameter ( Siegel et al, 1976 , 1984 ; Fuji et al, 1990 ; Ursino et al, 1992 ), exhibiting a frequency congruous with that of very low frequency oscillations present in, and correlated between, dynamic arterial blood pressure and splenic volume (see Barcroft and Nisimaru, 1932 ; Iriuchijima, 1984 ; Nisimaru, 1984 ). Differential vessel response latency to noradrenergic ( Christ, 1995 ; Seyrek et al, 2011 ), purinergic ( Alexander et al, 1999 ; Böhmer et al, 2010 ; Dǎnilǎ et al, 2017 ), and peptidergic excitatory sympathetic “neurono-vascular” synaptic drive may reflect differences in arteriolar diameter, architecture of the vascular tree, and mediator utilized at the smooth neuromuscular end-plate junction. Arterioloconstriction and venuloconstriction elicited by adenosine triphosphate elaborated from presynaptic end plates exhibit more rapid kinetics, compared with noradrenergic signaling.…”

P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases

“…Additional data from the mice model demonstrated that diet-induced T2D resulted in vascular inflammation and insulin resistance, accompanied by decreased eNOS-NO activity [ 53 , 56 ]. Sepsis-promoted endothelial dysfunction, monitored by the ex vivo examination, was also associated with reduced activity of eNOS-NO generation [ 57 ]. Therefore, it is suggested that amplifying the eNOS-NO signaling axis might decrease the inflammation-induced vascular damage observed in several CVDs.…”

Monoamine oxidase is a source of oxidative stress in obese patients with chronic inflammation

“…Hydrogen peroxide production was assessed in samples of visceral adipose tissue and branches of mesenteric arteries in the presence vs. absence of the MAO-A inhibitor, clorgyline (10 μM, 30 min incubation) using the Ferrous iron xylenol orange OXidation (FOX) assay (PeroxiDetect Kit, Sigma Aldrich) as previously described (Danila et al 2017;Lighezan et al 2016;Sturza et al 2015b;Sturza et al 2013a;Sturza et al 2015c;Sturza et al 2018;Utu et al 2017). The principle of the assay is that peroxides oxidize Fe 2+ to Fe 3+ ions at acidic pH.…”