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Current Enzyme Inhibition


ISSN (Print): 1573-4080
ISSN (Online): 1875-6662

Effect of Nitric Oxide Synthase Inhibition on Body Temperature Control During Endotoxemic Shock

Author(s): Evelin C. Carnio and Rafael S. Saia

Volume 4, Issue 1, 2008

Page: [10 - 17] Pages: 8

DOI: 10.2174/157340808783502531

Price: $65


Septic shock is a major cause of death following trauma and a persistent problem in surgical patients. It is a challenge to the critical care medicine specialist and carries an unacceptable high mortality rate, despite adequate antibiotic and vasopressor therapies. The prevalent hypothesis regarding its mechanism is that the syndrome is caused by an excessively defensive and inflammatory response. During the acute phase, some signaling mechanisms are activated, particularly changes in body temperature and hormonal release, which function to restore the host homeostasis that has been disturbed by the infection. Since the neuroendocrine and immune systems are functionally related, the exposure to antigens induces a synchronized response, which allows the organism to successfully endure immunologic changes. An important characteristic of this communication includes the appearance of proteins released into the circulation by activated immune cells. These proteins, called cytokines, may enter the circulation and reach neuroendocrine organs, where they either act, themselves or through the release of intermediates such as nitric oxide (NO). NO is a gaseous and free radical molecule, synthesized by nitric oxide synthases (NOS) during conversion of L-arginine in L-citrulline. These enzymes involve three different isoforms, neuronal, endothelial and inducible. The first and most common function attributed to NO is its role in controlling vascular tonus. Besides vasodilatation and antimicrobial defense, it has been demonstrated that NO has other functions, including body temperature control. The synthesis of NO may also be induced in the brain as a consequence of infection and may alter the function of the hypothalamic-pituitary axis. In this review we propose to discuss the pathophysiological effects of NOS inhibition in body temperature regulation during experimental sepsis and septic shock.

Keywords: Nitric oxide, thermoregulation, fever, hypothermia, vasopressin, lipopolysaccharide

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