• What do you understand by the term "endothelium-dependent" vasodilation? Explain

It is like the bradykinin increases the intracellular calcium levels in the endothelium. Then it leads to synthesis of NO in the endothelium therefore there is vasodilation. 

• When we talk about the NOS enzyme, what is meant by "constitutive" and "inducible" enzymes and what are the pathological and physiological implications. 

​​​​​​​The inducible are in macrophages and smooth muscles and they imerge  after a particular substance has been added. The constitutive are enzymes that are repetately synthesized irrespective of physiological needed. Because of their availability they have the most pathological and physiological importance. 

• Explain how No contributes to the fatal pathology of septic shock 

​​​​​​​The upregulation to NO leads to production of vast amount of NO, which contributes to pathogen elimination but also inappropriate vasodilation and to loss of vascular resistance

• Which autocoids mechanism of action depends on effects on the guanylyl cyclase-cGMP system?

​​​​​​​Nitric Oxide 

• No maybe be toxic to the cell. Which mechanism are available to the body to counter this detrimental effect of NO 

​​​​​​​it can react with hemooroteins which oxidizes NO to nitrates. It can also be inactived by the reaction with oxygen form nitrogen dioxide 

• Name a way in which NO can act pro-inflammatory. Give examples where it will have advantage of disadvantage 

​​​​​​​It is an immune regulator. Its advantage is that the synthesis of NO is helpful in protection of  injected parasites in animals after inhibition of iNOS. Its disadvantage is that in inflammatory conditions NO production may exacerbate tissue injury 

• In which possible neurological and psychiatric disease is NO involved?

Stroke 

Amyotrophic lateral sclerosis a

Parkinsons disease 

• In which diseases are angiotensinogen level increased? What are the implication of this?

Hypertension and Heart failure. Angiotensinogen will be converted to angitensin 1, which will then be converted again by ACE to angiotensin I. This stimulates vasoconstriction, increase glomerula hydrostatic pressure, increase blood volume due to fluid retention. 

• Why do drugs which inhibit the angiotensinogen system by acting on angiotensin receptors have fewer side effects that those that inhibit ACE 

​​​​​​​​​​​​​​It is because ACE inhibits the production of angiotensin I while the drugs that act on the angiotensin receptors only reduce the effect of angiotensin. Therefore the drug that inhibit ACE causes a deceased the breakdown of bradykinin which will then cause vasodilation leading to server dry caugh.

• In which way do ACE inhibitors have a two fold mechanism of action in the treatment of hypertension

​​​​​​​The ACE inhibitors inhibits the production of angiotensin I therefore it causes a decrease in aldesteron from the adrenal cortex which will lead to a decrease in Na reabsorption then water is excreted to reduce blood volume as well as blood pressure. ACE inhibitors also cause a decrease in ADH from the pituitary gland, decreasing water re tension by the kidneys reducing blood pressure. 

• At which type of angiotensin receptor do losartan and similar drugs act? Do they have any effect, direct or indirect at other angotensin ii receptors?

​​​​​​​Angiotesin i, they have an indrect effect on angiotensin ii receptors.

• What are the phycological effects of kininis on arteries and veins? Do other autocoids play a role in this action? Explain 

​​​​​​​They are potent vasodilators. They increase CAMP,NO,PG and DAG. Histimine have the same effect as it causes the vasodilation of arterioles and precapillary spintchers which decreases blood pressure. Serotonin has a different effect as it causes vasocinstriction. 

• Which receptor is probably the most involved in the important clinical effects of kinin?

​​​​​​​bradykinin 2 receptor 

• In which way are natriuretic peptides possibly effective in the treatment of hypertension, as well as congestive heart failure?

​​​​​​​The natriuretic peptides are released after tension on heart ventricles metabolized by neprylysin. They caused vasodilation which will decrease blood pressure, increase glomerula filtration and sodium ecxretion, decrease sodium reabsorption there decreasing the after load. 

• What is neprylisine and is the rationale for inhibiting its action in the treatment of heart failure? Can you name the drug being used as such? 

​​​​​​​Neprylisine is a neutral endopeptidisa responsible for degradation of natriuretic peptides in the kidney,liver and lungs. It decreases the circulation of ANP. Sacubitril inhibits neprilysin to increase the circulation of ANP and BNP thus causes natriusis and diuresis. ↓ afterload and blood pressure. 

• Give an example of endothelium-derived vasodilators and vasoconstrictors

​​​​​​​​​​​Vasodilatory: Substance P, CGRP, Vasomera 

Vasoconstriction: NPY 

​​​​​​​

Migraine it is a headache disorder characterised by recurrent headaches that are moderate to serve. Last for few hours to 3 days. Its episodes affect the one side of the head, pulsating in nature. Its side effects are nausea, vomiting and sensitivity to light. 

Treatment 

Ergotamine: it is the alpha1 and 5HT agonist. It selectively binds and activates 5HT receptors located on intracranial blood vessels, thereby resulting in vasoconstriction and reducing blood flow in cerebral arteries that may lead to relieve of vascular headaches.

Sumatriptan: It is a 5HT1d agonist. It selectively binds to and activates 5HT1D in the CNS it increases vasoconstriction, counteract vasodilation that causes pain during migraine. 

Aspirin: That inhibits the production of prostaglandin therefore causing an increase in production of leukotriene which causes vasoconstriction. Reducing pain.