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Modulation of nitric oxide production in human macrophages by apolipoprotein-E and amyloid-beta peptide.
They have been reported to show various pharmacological activities like anticancer [3, 4], antimalarial [5], anti-inflammatory [6], anti-tubercular [7], cytotoxic [8], gastroprotective [9], modulation of nitric oxide production [10] and so on.
Even though not fully understood, suggested mechanisms behind the described beneficial effects of intravenous vitamin C treatment, in both sepsis and burns, are scavenging of reactive oxygen species, reduction of endothelial adhesion molecules and modulation of nitric oxide production [3, 13 15].
Some previous studies indicate that the protective effect of GGA may be explained by its modulation of nitric oxide [32], [33].
Additionally, apoE is known to be involved in antigen presentation and modulation of nitric oxide production [ 100- 103].
AP displays various potentially beneficial actions including modulation of nitric oxide synthase [ 13] and dephosphorylation of extracellular ATP [ 23].
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Therapeutically, modulation of the nitric oxide pathway is a very promising goal.
In a rat model of septic shock, administration of APC prevented tumour necrosis factor-α mediated hypotension, probably caused by modulation of the nitric oxide response [ 20].
Ghrelin is capable of attenuating the hypotension caused by endotoxin, and we speculate that the improvement is due to modulation of cytokines, nitric oxide and augmented vasopressin blood levels.
Ghrelin has been shown to cross the blood brain barrier [ 14]; thus, it is possible that serum ghrelin may cross the blood brain barrier and promote memory formation through dose-dependant modulation of the nitric oxide production.
Adiponectin and adipocyte-derived relaxing factors are released by perivascular fat to decrease contractile responses to vasoconstrictive agents, thus exerting a protective antihypertensive function via the control of endothelium-dependent (modulation of the nitric oxide-to-endothelin-1 ratio) and independent mechanisms (cell hyperpolarization, and production of ROS, hydrogen peroxide) (25, 26).
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