Endothelial cells respond to vasorelaxants by releasing EDRF that act on vascular muscle to cause relaxation and consequently vasodilitation. Thus for vasodilation to occur it is dependent on the endothelium.
A "constitutive" enzyme is an enzyme that is formed at a constant rate and amout in a cell. A "inducible" enzyme is an enzyme that is only produced in the presence of their substrate thus the production is not constant. The iNOS (inducible) is not normally readily detectable until inflammatory mediators induce iNOS gene transcription that results in synthesis of to much NO, because of the accumulation of iNOS. The constitutive NOS enzyme forms at a constant rate and is not trigered or regulated by calsium.
Cytokines induce synthesis of iNOS during an infection. It causes a widespread generation of NO which results in exaggerated hypotension, shock and death. This leads to septic shock and can be treated by the inhibition of NOS or compounds that prevent the action of NO. There is no improvement in survival in patients with gram-negative sepsis that is treated with NOS inhibitors, despite the ability of NOS inhibitors to ameliorate hypotension in sepsis treatment.
Guanylyl Cyclase is converted to Activated Guanylyl Cyclase by adding NO and Activated Guanylyl Cyclase changes GTP to cGMP.
NO reacts with the iron in hemoglobin in the blood and can therefore be inhibited by hemoglobin who is always present in the body.
When infection and injury occurs it leads to an increase in leukocytes, and inflammatory mediators and causes an increase in iNOS which results in higher levels of NO. This causes inflammation. The advantages is that NO, with interaction with superoxide, is a microbicide. NO also protects the body via immune cell function. It also stimulates the synthesis of inflammatory prostaglandins. The disadvantages are exacerbation of tissue injury, psoriasis lesions, airway epithelium in asthma and inflammatory bowl lesions.
Stroke, amyotrophic lateral sclerosis and Parkinson's disease.