Nitric Oxide at the cross-road of immunoneuroendocrine interactions

BESUHLI DE RETTORI V; DE LAURENTIIS A

Rio de Janeiro, Brazil

Congreso; VII ISNIM Congress; 2008

International Society for Neuroimmunomodulation

Nitric Oxide (NO) normally produced by the constitutive isoform of NO synthase (NOS) is a key modulator of many physiological functions acting as an autocrine or paracrine cellular mediator. NO have profound biological effects in the nervous and immune systems and plays a crucial role in reproduction. In the brain, NO activates the release of luteinizing hormone-releasing hormone (LHRH) that evokes the lordosis reflex in female rats. In males, activation of NOergic terminals that release NO in the penis induces erection by generation of cyclic guanosine monophosphate (cGMP). Also, the LHRH that reaches the pituitary gland induces the release of gonadotropins by activating neural NOS. In the gonad, NO participates in the induction of ovulation and in causing luteolisis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins. NO produced by the inducible NOS participates in the pathophysiology of inflammation and infection leading to sepsis and septic shock. Lipopolysaccharides and cytokines can induce it in the endothelium, vascular smooth muscle cells, macrophages and different parenchymal cells. This large increase in NO leads to the production of inflammatory mediators which can be deleterious to the normal homeostasis. NO increases the production of cGMP and activates cyclooxigenase and lipoxygenase with production of prostaglandin E and leukotrienes, respectively. Furthermore, cytokines induced in neurons activate neuronal NOS and NO released determines the pattern of hypothalamic-pituitary secretion which characterizes infection. Also, cytokines act directly in the pituitary gland, in part, via inducible NOS, inhibiting the release of hormones. Thus, NO plays a key role in the immunoneuroendocrine interactions in physiological and pathophysiological conditions. Grants PICT03-14264 and PIP 6149.