Blog#2.2

• In any disease conditions that prevent increased blood pressure (hypertension) and it increases the feeling of thirst, which stimulates the desire for salt, stimulates the release of other hormone involved by fluid retention. It also finds heart faluire. The overactive RAAS causes an increase in angiotensinogen levels. Too much angiotensin can cause the body to retain too much fluid or to have elevated blood pressure levels not caused by other problems. High angiotensin levels can also cause the heart to grow, leading toheart failure. 

• ​Drugs which blocks ACE will also lead to the inhibition of bradykinin breakdown. Increased bradykinin concentrations cause bradykinin 2 receptor mediated bronchoconstriction (a vagal cough reflex) which cause the negative side-effect of a dry, irritating cough. Drugs which act specifically on angiotensin receptors will not inhibit bradykinin breakdown and thus will not have this adverse effect because of increased bradykinin.

• ​ACE inhibitors firstly block the conversion of angiotensin I to angiotensin II. Angiotensin II type I receptors are also blocked. This leads to vasodilation instead of vasoconstriction which leads to a decrease in peripheral resistance and BP. Aldosterone secretion decreases which leads to less salt and water retention and more excretion which lowers cardiac preload, decrease cardiac output and decrease BP. Left ventricular hypertrophy is also reversed. ACE inhibitors also inhibit bradykinin breakdown. Increased bradykinin concentrations, increase prostaglandin synthesis which increase arterial vasodilation, lowers peripheral resistance and lowers BP. This is all therapeutically useful in hypertension.
• Angiotensin II receptor antagonist. The action on the AT1 receptors is direct, but the action on aldosterone is indirect.
• Kinins cause vasodilation, edema, and contraction of smooth muscle, as well as pain and hyperalgesia through stimulation of C-fibers. They are formed from high and low molecular weight kininogens by the action of serial protease kallikreïen in plasma and peripheral tissues.
• B1 and B2 bradykinin receptors.
• These peptides cause effects such as diuresis, natriuresis, vasodilation, and inhibition of aldosterone synthesis and renin secretion as a circulating hormone, and thereby play an important role in regulating blood pressure and blood volume. Increases Glomerular Filtration and Na Excretion. Decreases Renin release and Aldosterone mechanism (decreases Na reabsorption) and inhibits angiotensin II. It can prevent edema and hypertension. 
• It is a neutral endopeptidase which is responisble the breakdown of natiuretic peptides in the kidney liver and lungs. Inhibition of this increases circulating levels of ANP and BNP and thus causes natriuresis and diureses. (Sacubitril)
• Vasodilators: PGI₂ & NO; Vasoconstrictors: Endothelin - ET₁, ET₂, ET.