Vascular Sympathetic Neurotransmission and Endothelial Dysfunction

Abstract

Endothelium is an important regulator of vascular tone via release of various endotheliumderived substances. Several studies have reported that endothelium may decrease the release of noradrenaline from vascular postganglionic sympathetic nerves and thus neurogenic vasoconstriction. Endothelium derived-mediators (adenosine and NO) can modify vascular sympathetic neurotransmission and are relevant for vascular homeostasis. This is a relevant issue in terms of vascular homeostasis and, any modification, may lead to a deregulation process and to pathologies. Focus on NO-mediated effects on vascular sympathetic transmission will be done, discriminating the effects ascribed to NO generated by NO synthases located in the different vascular layers. A comparison between mesenteric/ tail arteries will also be explored, particularly the relevance of the transsynaptic modulation on noradrenaline release mediated by endothelial NO and adenosine in normotensive/ hypertensive vascular tissues. Adenosinergic system, namely adenosine, nucleoside transporters and adenosine receptors, can be influenced by endothelium mediators, namely by NO, causing alterations on the way these players interact with each other. In conditions where endothelium is compromised, a deregulation occurs with an increase in vascular sympathetic neurotransmission (as a consequence of adenosinergic system dynamic alteration). In summary, the impact of endothelial dysfunction on vascular neurotransmission is debated with particular focus on adenosinergic and nitroxidergic system dynamics.

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling

“…Under conditions of elevated BP, the adventitia becomes the predominant wall component due to the profound influence on intima and media function in disease [40,61]. As so, our work corroborates others' findings and demonstrates the importance of adventitia, suggesting a modulatory role on vascular function [48].…”

“…Some studies demonstrate that adventitia is the most complex compartment of the vessel that integrates key regulators of vessel wall function [40,47] and data evidence that wall changes in the adventitia occur early in the course of vascular disease development before changes are seen in the intima or the media [17]. In the literature, the influence of intima to media layers and vice versa is well established: endothelial cells can release mediators that alter the tonus of VSMC, and VSMC can also influence the activity of endothelial cells [48]. Recent data has also highlighted the interplay of intima with adventitia since endothelial cells have been shown to release mediators able to alter vascular sympathetic tonus [39,48,49].…”

“…In the literature, the influence of intima to media layers and vice versa is well established: endothelial cells can release mediators that alter the tonus of VSMC, and VSMC can also influence the activity of endothelial cells [48]. Recent data has also highlighted the interplay of intima with adventitia since endothelial cells have been shown to release mediators able to alter vascular sympathetic tonus [39,48,49].…”

“…In fact, the remodeling of mesenteric vessels was previously associated with increased levels of ROS (measured by dihydroethidium (DHE) in the adventitia [54]. Moreover, previous data suggested that superoxide anion release from the adventitia might reduce endothelial NO bioavailability [48,55], which would also enhance vasoconstriction and increase resistance. Interestingly, it has been demonstrated that an increased ROS is a primary mechanism whereby Ang II causes an increased sympathetic nervous system activity in a complex mechanism involving the contribution of the adaptive immune response [56].…”

Serratiopeptidase Attenuates Lipopolysaccharide-Induced Vascular Inflammation by Inhibiting the Expression of Monocyte Chemoattractant Protein-1

“…Nitric oxide (NO), prostacyclin, and endothelial-derived hyperpolarizing agents are all vasodilators. Endothelin-1, angiotensin II (Ang II), and thromboxane A2 are vasoconstrictors [ 18 , 19 , 20 ]. Serratiopeptidase (SRP) is created from Serratia microorganisms that reside in the intestines of the silkworm (Bombyx mori), which is why it is usually known as the “silkworm enzyme” [ 21 ].…”