Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D05731 (Rimonabant)
 326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipose tissue is an active and complex endocrine organ that secretes numerous bioactive substances, including hormones, growth factors, and cytokines. Central obesity, one of the components of metabolic syndrome, is a cardiometabolic risk factor associated with a state of chronic inflammation and coagulation, one in which the expression of certain adipocytokines, including tumor necrosis factor-alpha (TNF-(alpha), interleukin (IL)-6, and plasminogen activator inhibitor-1 (PAI-1) is more abundantly increased, while adiponectin expression is decreased. TNF-alpha initiates and organizes inflammatory changes in vascular tissue. IL-6, an inflammatory cytokine directly implicated in atherogenesis, exerts pleiotropic effects on a variety of tissues. An increased concentration of PAI-1, an important regulator of the endogenous fibrinolytic system, promotes continued clotting. Adiponectin, on the other hand, has potent vasculoprotective, angiogenic, anti-inflammatory, and antiatherogenic properties. Adiponectin levels are low in obese individuals and increase when weight is lost, thereby serving as a marker for cardioprotection. Weight loss has long been promoted as a means to reduce the risk of type 2 diabetes and cardiovascular disease; for example, exercise and a hypocaloric diet have been shown to decrease PAI-1 levels. Weight loss drugs, such as orlistat, a lipase inhibitor, and sibutramine, a serotonin and norepinephrine reuptake inhibitor, have both been shown to produce a decrease in C-reactive protein levels and an increase in serum adiponectin. Rimonabant, a selective cannabinoid 1 receptor antagonist in Phase III studies, also has been shown to increase adiponectin levels. These agents may play a role in the regulation of adipocytokines, which may directly affect the risk for cardiometabolic disease.
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PMID:The relation of adipose tissue to cardiometabolic risk. 1720 62

It is widely assumed that LPS lowers arterial pressure during sepsis by stimulating release of TNF-alpha and other vasoactive mediators from macrophages. However, recent data from this and other laboratories have shown that LPS hypotension can be prevented by inhibiting afferent impulse flow in the vagus nerve, by blocking neuronal activity in the nucleus of the solitary tract, or by blocking alpha-adrenergic receptors in the preoptic area/anterior hypothalamic area (POA). These findings suggest that the inflammatory signal is conveyed from the periphery to the brain via the vagus nerve, and that endotoxic shock is mediated through a central mechanism that requires activation of POA neurons. In the present study, we tested whether central cannabinoid 1 (CB1) receptors participate in the control of arterial pressure during endotoxemia based on evidence that hypothalamic neurons express CB1 receptors and synthesize the endogenous CB anandamide. We found that intracerebroventricular administration of rimonabant, a CB1 receptor antagonist, inhibited the fall in arterial pressure evoked by LPS significantly in both conscious and anesthetized rats. Rimonabant attenuated both the immediate fall in arterial pressure evoked by LPS and the second, delayed hypotensive phase that leads to tissue ischemia and death. Rimonabant also prevented the associated LPS-induced rise in extracellular fluid norepinephrine concentrations in the POA. Furthermore, rimonabant attenuated the associated increase in plasma TNF-alpha concentrations characteristic of the late phase of endotoxic hypotension. These data indicate that central CB1 receptors may play an important role in the initiation of endotoxic hypotension.
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PMID:Central cannabinoid 1 receptor antagonist administration prevents endotoxic hypotension affecting norepinephrine release in the preoptic anterior hypothalamic area. 1929 73