Dexmedetomidine and regulation of splenic sympathetic nerve discharge.

Recent lines of inquiry indicate that sedatives can influence the immune system, leading to the concept of sedative-induced immunomodulation. It has been hypothesized that sedatives may alter immune responses by modulating the sympathetic nervous system, however, little information is known regarding the effects of sedatives on regulation of splenic sympathetic nerve discharge (SND), a significant omission based on the functional role that changes in splenic SND exert on splenic cytokine gene expression. The present investigation determined the effect of systemic Dexmedetomidine (Dex) administration on the level of directly-recorded splenic SND and tested the hypothesis that the intravenous administration of Dex would inhibit splenic SND in anesthetized rats. The present results demonstrate for the first time that intravenous Dex administration significantly reduces splenic sympathetic nerve outflow in baroreceptor-intact and sinoaortic-denervated rats, indicating that Dex administration alters the central regulation of splenic SND. The present results provide new information regarding the effect of a centrally-acting alpha2-adrenergic agonist on the level of sympathetic nerve outflow to a secondary lymphoid organ that plays a critical role in peripheral immune responses.

Emerging role of epoxyeicosatrienoic acids in coronary vascular function.

The importance of endothelium-derived nitric oxide in coronary vascular regulation is well-established and the loss of this vasodilator compound is associated with endothelial dysfunction, tissue hypoperfusion and atherosclerosis. Numerous studies indicate that the endothelium produces another class of compounds, the epoxyeicosatrienoic acids (EETs), which may partially compensate for the loss of nitric oxide in cardiovascular disease. The EETs are endogenous lipids which are derived through the metabolism of arachidonic acid by cytochrome P450 epoxygenase enzymes. Also, EETs hyperpolarize vascular smooth muscle and induce dilation of coronary arteries and arterioles, and therefore may be endogenous mediators of coronary vasomotor tone and myocardial perfusion. In addition, EETs have been shown to inhibit vascular smooth muscle migration, decrease inflammation, inhibit platelet aggregation and decrease adhesion molecule expression, therefore representing an endogenous protective mechanism against atherosclerosis. Endogenous EETs are degraded to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase. Pharmacological inhibition of soluble epoxide hydrolase has received considerable attention as a potential approach to enhance EET-mediated vascular protection, and several compounds have appeared promising in recent animal studies. The present review discusses the emerging role of EETs in coronary vascular function, as well as recent advancements in the development of pharmacological agents to enhance EET bioavailability.