What is Sepsis?  Nitric Oxide

      
       

 

          
       

The endothelium is an endocrine organ, capable of regulating the function of the microcirculation. The most important compound produced is nitric oxide (NO) (13), an endogenous vasodilator (it is the mechanism by which nitrate drugs work). Its major effects are to cause local vasodilatation and inhibition of platelet aggregation. Nitric Oxide is produced from l-arginine by nitric oxide synthetase (NOS), and its actions are mediated by cGMP. NO is an essential to the normal functioning of the vascular system. So what happens in sepsis? It appears that there are two forms of the enzyme nitric oxide synthetase, a constitutive form, produced as part of the normal regulatory mechanisms, and an inducible form, whose production appears to be pathologic. Inducible NOS (iNOS) appears to be produced as an offshoot of the inflammatory response, by TNF and other cytokines. It results in massive production of nitric oxide, causing widespread vasodilatation (due to loss of vasomotor tone) and hypotension, which is hyporeactive to adrenergic agents.

Nitric oxide has a physiological antagonist, endothelin-1, a potent vasoconstrictor whose circulating level is increased  in cardiogenic shock and following severe trauma.

Nitric oxide has a physiological antagonist, endothelin-1, a potent vasoconstrictor whose circulating level is increased  in cardiogenic shock and following severe trauma.

The major cause of vasodilation in sepsis appears to be mediated by ATP-sensitive potassium channels in smooth muscle. We do not know for certain what agents cause activation of these channels. The result of activation is increased permeability of vascular smooth muscle cells to potassium, and hyperpolarization of the cell membranes (8;9;9) , preventing muscle contraction, leading to Vasodilation.

In addition to potassium channels and inducible nitric oxide, there is a relative deficiency of vasopressin in early sepsis, the cause and significance of which is unknown (14).

References

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THIS TUTORIAL BY PATRICK NELIGAN MD, UNIVERSITY OF PENNSYLVANIA

        
       

 

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