Nitric oxide and endothelin in pathophysiological settings

Abstract

The role of the endothelium is now known to encompass the generation of many potent cytokines which impact endothelial cells, adjacent tissue such as smooth muscle cells, and distant sites in an autocrine, paracrine, and endocrine manner, respectively. This review addresses two of these cytokines, nitric oxide and endothelin, and describes how each effects the functions of endothelial cells, including regulation of platelet aggregation and coagulation, regulation of vasomotor tone, modulation of inflammation, and the regulation of cellular proliferation. The emphasis is on the increasingly recognized importance of the autocrine and paracrine mechanisms by which nitric oxide and endothelin act. In particular, autoinduction of endothelin is proposed as a central mechanism underlying endothelin's renowned effects. Additionally, specific nitric oxide/endothelin interactions are discussed by which each cytokine modulates the production and actions of the other. The net effect observed in a variety of physiological and pathophysiological settings, therefore, reflects a balance of these opposing functions.

Inducible nitric oxide synthase suppresses the development of allograft arteriosclerosis.

“…Animals were randomized to receive either CsA (10 mg/kg/d) or saline injections daily for 2 d, after which the animals were killed, and the thoracic aortas were harvested. Semiquantitative RT-PCR using 32 Plabeled iNOS primers was performed on RNA isolated from the aortas. Detection of ␣-actin served as a control for cDNA synthesis.…”

“…Again, this raises the possibility that intramural iNOS expression directly suppresses intimal hyperplasia. NO has also been implicated in the tissue injury associated with several chronic inflammatory and autoimmune diseases, such as diabetes mellitus and rheumatoid arthritis (32). Thus, the question that arises is whether the potentially cytotoxic actions of NO or its reaction products perpetuate the pathogenesis of allograft arteriosclerosis or whether the antiatherogenic properties of NO suppress the development of neointimal hyperplasia and impede the development of chronic rejection in cardiac allografts.…”

Pathogenetic aspects of circulation and hidration and acid-base statuses in the clinical course of toxic epidermal necrolysis

“…При цих станах охарактеризована загальна спрямова-ність змін обміну речовин, більш детально при ТЕН [5][6][7], однак відомості про порушення, гідратаційно-циркуляційного та кислотно-основного стану (КОС), одиничні та суперечливі [8][9][10].…”

S-Glutathionylation Reshapes Our Understanding of Endothelial Nitric Oxide Synthase Uncoupling and Nitric Oxide/Reactive Oxygen Species-Mediated Signaling

“…This process involves the calcium/calmodulin-regulated transfer of electrons from NADPH through a flavin adenine dinucleotide (FAD)-and flavin mononucleotide (FMN)-containing reductase domain to the heme of the l-arginine-binding oxygenase domain, which also binds tetrahydrobiopterin (BH 4 ) (6, 30). In the absence of BH 4 , NO synthesis is abrogated, and instead, O 2 -is generated (43,50).NO is involved in a number of roles within the endothelium, regulating vascular tone, vascular growth, platelet aggregation, and modulation of inflammation (23,29,32). As such, endothelial dysfunction produced by a decrease in bioavailable NO is a characteristic feature in many disease states, and one of the mechanisms underlying this dysfunction is the production of reactive oxygen species (ROS) in the vasculature (2,35,48).…”

“…NO is involved in a number of roles within the endothelium, regulating vascular tone, vascular growth, platelet aggregation, and modulation of inflammation (23,29,32). As such, endothelial dysfunction produced by a decrease in bioavailable NO is a characteristic feature in many disease states, and one of the mechanisms underlying this dysfunction is the production of reactive oxygen species (ROS) in the vasculature (2,35,48).…”