What do you understand by the term “endothelium-dependent” vasodilation?  Explain.

This is done by increasing shear stress on the endothelium. increase in blood flow stimulates endothelium-dependent vasodilation

When we talk about the NOS enzyme, what is meant by “constitutive” and “inducible” enzymes and what are the pathological and physiological implications thereof?

• eNos and nNOS are both constitutive enzymes. Both need to be activated. Activation occurs when NO synthesis is triggered by agents which then increases cytosolic calcium concentrations. The cytosolic calcium forms complexes with calmodulin which then binds and activates these two enzymes. Thus they are calcium dependant and readily detectable and release from various cell types
• iNOS is an inducible enzyme, meaning it’s not regulated by calcium, but is active after synthesis.It is not readily detectable until inflammatory mediators induce the transcription of the iNOS gene – resulting in its accumulation and large quantities of NO. It is calcium independent and released from smooth muscle and Macrophages.

Explain how NO contributes to the fatal pathology of septic shock.

• Septic shock is a life-threatening condition caused by sever localised or wide spread infection that requires medical attention. Sepsis usually means that the infection has spread into the blood stream and is now affecting every organ within the body.
• Sepsis is an inflammatory response due to a serious infection. The infection usually triggers cytokines to release iNOS in macrophages, neutrophils, and T-cells, as well as hepatocytes, smooth muscle cells , endothelial cells and fibroblasts.
• The widespread release of NO leads to exaggerated Hypotension, shock and in extreme cases – death. NO is a potent vasodilator, thus the exaggerated vasodilation would have lead to exaggerated hypotension

Which autacoids’ mechanism of action depends on effects on the guanylyl cyclase-cGMP system?

Nitric oxide. Nitric oxide activated the conversion of guanylyl cyclase to activated guanylyl cyclase, this will eventually lead to the conversion of GTP to cGMP. The elevation of cGMP will lead to vasodilation and relaxation of smooth muscle.

NO may be toxic to the cell.  Which mechanisms are available to the body to counter this detrimental effect of NO?

Arginase is an enzyme in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. It suppresses nitric oxide.

Name a way in which NO can act pro-inflammatory.  Give examples of where it will have advantages or disadvantages.

• During the infection there is An increase in iNOS levels. No has a pro-inflammatory effect in the TH1 cell function and by stimulating the synthesis of inflammatory  prostaglandins by activiating COX2
• Advantages are its direct vasodilatory effects and other mechanisms that lead to erythema, vascular permeability and subsequent edema.
• Disadvantages lie in long term effects due to chronic inflammation such as exacerbation of tissue injury such as psoriasis lesions, airway epithelium in asthma and inflammatory bowel lesions. It May also exacerbate arthritis.

In which possible neurological and psychiatric diseases is NO involved? 

physiological functions such as noradrenaline and dopamine releases

diseases: schizophrenia, bipolar disorder