Hypertension and the Renin-Angiotensin-Aldosterone System
Renin-Angiotensin-Aldosterone System
The renin-angiotensin-aldosterone system, otherwise known as RAAS is a complex hormone system that regulates blood pressure and fluid balance in the human body. When blood volume is low, juxtaglomerular cells in the kidneys activate prorenin, which secretes renin directly into the blood stream circulation. Subsequently, a drop in blood volume additionally releases angiotensinogen from liver, in which renin converts into angiotensin I. Angiotensin I is then converted to angiotensin II through the enzyme angiotensin converting enzyme (ACE) found in the lung. Angiotensin II is a potent biological compound that causes blood vessels to constrict, resulting in an increase in blood pressure. Additionally, angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Furthermore, thirst or antidiuretic hormone can effectively stimulates the pituitary gland, which could release corticotropin-releasing hormone stimulating the adrenal cortex and thereby releasing aldosterone. Aldosterone contributes to the RAAS system by causing the tubules of the kidneys to increase the reabsorption of sodium and water back into the blood stream. Thus, an increase in the reabsorption of water, increases the volume of fluid in the body, which increases the blood pressure. Once the blood volume and blood pressure stabilizes, these collective effects triggers a negative feedback which essentially shutdown the production of renin, effectively decreasing the production of angiotensin II and aldosterone. High potassium leftover in the bloodstream will decrease sodium and water reuptake in the body and therefore decrease fluids in the blood stream and thus lowering blood pressure.
Medicines
Due to the importance of the renin-angiotensin-aldosterone system in regulating blood pressure, many medical drugs and research have been developed to interrupt different steps in this system to lower blood pressure. These drugs are the main ways to control hypertension, heart failure, kidney failure, and harmful effects of diabetes.
Angiotensin-converting-enzyme inhibitor (ACE inhibitor) is a pharmaceutical drug used primarily for the treatment of hypertension, congestive heart failure, or renal complications due to diabetes. Common prescribe ACE inhibitors include perindopril, captopril, enalapril, Lisinopril, and ramipril. This group of drugs causes dilatation of blood vessels, which results in lower blood pressure. Additionally, ACE inhibitors stops the formation of angiotensin II by inhibiting the angiotensin-converting enzyme, thereby, decreasing the tension in the blood vessels and lowering the blood volume, thus lowering blood pressure. Despite the effects of ACE inhibitors, often times, these drugs are coupled with other drugs such as beta blockers and calcium channel blockers in combating hypertension and congestive heart failure.
Angiotensin receptor blockers (ARBs) or angiotensin II receptor antagonists is a pharmaceutical drug similar in the function of ACE inhibitors in treating hypertension, congestive heart failure, or renal complications due to diabetes. Common drugs that prescribe ARBs are valsartan, telmisartan, losartan, irbesartan, olmesartan, eprosartan, and candesartan. ARBs functions by blocking the receptor sites for angiotensin II, thus nullifying the bio-active compound’s effects. In all, one of the rational for using ARBs as oppose to ACE inhibitors is the avoidance of dry cough commonly found as a side effect of ACE inhibitors.
Renin inhibitors are a group of pharmaceutical drugs mainly used in the treatment of hypertension. Essentially, renin inhibitors blocks renin’s ability of converting angiotensinogen to angiotensin I, subsequently inhibiting angiotensin II activity, thus regulating the RAAS from increasing blood pressure and fluid reuptake.
Loop diuretics are a group of pharmaceutical diuretic drugs used in primarily in the treatment of hypertension and edema due to congestive heart failure or renal insufficiency. Common drugs prescribed are furosemide, bumetanide, ethacrynic acid, and torsemide. These group of diuretic drugs act at the ascending loop of Henle in the kidney, primarily in the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption. By disrupting the reabsorption of magnesium and calcium, this prevents the generation of a hypertonic renal medulla. A lack of concentrated medulla, water has less of an osmotic driving force to leave the collecting duct system. In all, this increase urine production and less reabsorption in the blood stream, thus decreasing blood pressure.
Thiazide is a class of diuretics used to treat hypertension and edema. Thiazide is a class of diuretics derived from benzothiadiazine. They control hypertension in part by inhibiting reabsorption of sodium and chloride ions from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive sodium-chloride symporter. A decrease in the reabsorption of sodium and chloride ions will decrease water intake and thus decreasing blood pressure in the blood stream.
Chinese Medicine Recent researches shown that excessive RAAS activation not only causes sustained increases in blood pressure but also leads to arterial vasoconstriction, fibrosis and cardiac remodeling. Angiotensin II are involved in vasoconstriction as well as the proliferation and migration of smooth muscle cells, formation of foam cells, aggregation and adhesion of platelets, bradykinin degradation, nitric oxide reduction and endothelin increases by acting on AT1R. AT1R activation can cause arterial vasoconstriction, smooth muscle cell proliferation and strengthen myocardial contraction, which can lead to hypertension, vascular remodeling and cardiac hypertrophy. Several studies shown that Qingxuanjiangya decoction and Qingxin capsule could safely and effectively lower blood pressure in patients with mild or moderate degrees of hypertension, improve their clinical symptoms and more effectively improve their quality of life. This mechanism might be related to their ability to inhibit the activity of the circulatory renin–angiotensin system. Additionally, Xiaxi oral liquid lowers BP and the content of myocardial AT1Rs by down-regulating the expression of AT1 mRNA, thus leading to decreased blood pressure. Another type of Chinese medicine is Niuhuangjiaangya pill, which has an antihypertensive effect by directly blocking AT1R and indirectly activating angiotensin II type 2 receptor.