Renin Release of antidiuretic hormone ADH

Introduction
The renin-angiotensin-aldosterone system (RAAS) plays a very important role in the regulation of systemic vascular resistance and blood volume. Its role helps ensure hemodynamic stability when the body loses water, salt, and blood. The baroceptor reflex always corrects these imbalances in a short-term window while the RAAS helps keep the balance when the imbalances are chronic. The RAAS is made up of three main compounds: angiotensin II, aldosterone, and rennin (Weir & Dzau, 1999). The three compounds help in the elevation of blood pressure when renal blood pressure decreases and when there is a decrease in the delivery of salt to the distal convoluted tube. It also increases arterial pressure during beta-agonism. Its characteristics and functions make it possible for the body to regulate blood pressure for long periods of time. While it is mainly linked to the kidneys, its functions also have effects on the adrenal glands, blood vessels, the heart, and the brain.
The Mechanism
Afferent arterioles found in the kidney have specialized cells referred to as juxtaglomerular (JG) cells. The JG cells carry prorenin which is secreted in its inactive form. Its activation in the JG Cells turns it into renin. Its activation is usually triggered by beta-activation or a decrease in blood pressure. The activation may also be due to a response to the reduction of sodium load present in the distal convoluted tubule.
As renin enters the bloodstream, it begins to act on angiotensinogen which is usually produced by the liver and can be found in blood circulation in the plasma. The action of renin on angiotensinogen cleaves it into angiotensin I which is a precursor for angiotensin II. Angiotensin I is naturally inactive (Fountain & Lappin, 2018; Weir, M.R., & Dzau, V.J. (1999).
During the process through which angiotensin I is converted to angiotensin II, an enzyme referred to as angiotensin-converting enzyme (ACE) acts as the catalyst. ACE is mainly found in the lungs’ and the kidneys’ vascular endothelium. On angiotensin I being converted to angiotensin II, it binds itself to angiotensin type I and angiotensin type II thereby affecting the brain, kidneys, arterioles, and the adrenal cortex. It is not yet known conclusively what the type I and type II (AT) receptors roles are. Nonetheless, there is evidence that they have a role in vasodilation through the generation of nitric oxide. While in the plasma, the half-life of angiotensin II is 1 to 2 minutes and then it is degraded by peptidases into angiotensin III and IV (Fountain & Lappin, 2018). It has been shown that angiotensin has all the stimulating properties of angiotensin II but only 40 percent of angiotensin II’s pressor effects. The systemic effect of angiotensin IV is reduced.
Angiotensin II increases the reabsorption of sodium in the kidney’s proximal convoluted tubule by increasing Na-H exchange. When sodium levels rise in the body, the blood’s osmolarity increases and this leads to fluid shifting to extracellular space and the blood volume. The increase in blood volume results in high arterial pressure.
The adrenal cortex, particularly the zona gloerulosa, is also acted upon by angiotensin II where it helps in the stimulation of aldosterone release. Aldosterone’s function is to help in the excretion of potassium and the reabsorption of sodium at the nephron’s collecting duct and at the distal tubule. It does this by helping stimulate the insertion of basolateral Na –K ATPase proteins and luminal Na channels. The effect is that reabsorption levels of sodium increase significantly. As mentioned previously, an increase in sodium levels leads to an increase in the blood’s osmolarity which subsequently leads to a rise in ECF and blood volume (Fountain & Lappin, 2018; Carey, 2015). Aldosterone is different from angiotensin II in that it is effectively a steroid hormone. Therefore, it brings change by acting to bind to nuclear receptors and moving to alter gene transcription. This makes the effects aldosterone has to take hours to days to start. Angiotensin II, on the other hand, has very rapid effects.
Angiotensin II’s effects on vasoconstriction occur in the systemic arterioles. At this point, it moves to bind itself to G protein-coupled receptors thereby resulting in a secondary messenger cascade which causes potent arteriolar vasoconstriction. These actions lead to total peripheral resistance increase which in turn leads to blood pressure increasing.
Lastly, angiotensin II has three effects on the brain. The first effect is that it binds itself to the hypothalamus to promote an increase in the intake of water by stimulating thirst. The second effect is that it stimulates the posterior pituitary to release antidiuretic hormone (ADH) (Fountain & Lappin, 2018). Antidiuretic hormone is also known as vasopressin and it moves to increase reabsorption of water by the kidneys. It does this by having aquaporin channels inserted at the collecting duct. The third effect on the brain is that it reduces baroreceptor reflex’s sensitivity and this helps reduce its response to rising blood pressure levels, responses which could be counterproductive to the objectives of the RAAS. In totality, the three effects result in an increase in the levels of body water, vascular tone, and sodium in the body.
Processes Triggered When There is Heart Failure or When a Patient Experiences Hypovolemic State
The RAAS main function in the body is to regulate fluid balance and blood pressure. The RAAS hormone system is activated by hypovolemia through a series of actions that end in the production of angiotensin II (Ang II). Ang II helps increase blood pressure, stimulate drinking, and increase the ability of the kidney tubules to reabsorb sodium and so restore the volume of blood. Different angiotensin lengths (Ang 1 -7) bind themselves to AT1, AT2, AT4, and Mas receptors to help initiate various antagonistic pathways that ensure a balanced status (Carey, 2015). Aside from the systemic function, RAAS has also been shown to have autocrine, intacrine, and paracrine roles in cell and tissue levels. When RAAS activity is at abnormal levels, it leads to hypertension, a situation that can be accompanied with renal failure, thrombosis, fibrosis, etc. In a scenario like this, there may be a need for the inhibition of ACE. This inhibition can be done by using an inhibitor like captopril which reduces Ang II’s production. This is an effective clinical treatment of various cardiovascular abnormalities including hypertension.
Heart failure is today classified as a complex syndrome and it involves a lot of different conditions. Some of the conditions include RAAs activation, overexpression of brain natriuretic peptide (BNP) and the ANP, an increase in the vasopressin release, tumor necrosis factor, and endothelin-1 (Otte & Spier, 2009). A reduction in cardiac output and a decrease in blood pressure lead to the activation of the adrenergic nervous system thereby causing an increase in heart rate, an increase in myocardial contractility, and peripheral vasoconstriction. The actions lead to an increase in blood flow to the vital centers. Nonetheless, when the adrenergic nervous system is chronically activated various conditions such as cell dysfunction, cell death, myocardial hypertrophy, tachycardia, arrhythmias, fibrosis, and peripheral vasoconstriction may occur.
RAAS plays a very important role in cardiac function especially in the progression of the HF. When it is activated in the heart, it triggers direct cardiac injury and accelerated atherosclerosis that comes as a result of the activation of several pathogenic pathways. Also, many studies have shown that actions that lead to RAAS blockade can prevent or attenuate cardiac damage even when the blood pressure doesn’t come down. ACE2 is a glycoprotein that can be found in most of the body’s tissues with the kidney being one of the places it is dominantly present. It is also highly expressed in the heart and the endothelium. It is the primary metabolism pathway in the heart for AII. When it is deficient, conditions such as progressive cardiac fibrosis and early cardiac hypertrophy may result. These conditions may result in diastolic dysfunction as cardiac pressure overloads or as people age (Macia-Heras et al., 2012). In a failing human heart, ACE2 expression generally increases. This also applies to the levels of A (1 – 7). There has been research done recently on mice showing that increasing the activity of ACE2 may have therapeutic benefits in settings where AII is overactive.
In all, it appears that ACE and ACE2 balance in the heart and the subsequent counterbalancing of AI and A (1-7) are the main factors that drive hypertension and progressive cardiac disease. Data from research done in the area gives support to hypotheses that when the activity or expression of A(1-7) decreases, the cardiovascular system is rendered more vulnerable to AII’s pathological actions (Macia-Heras et al., 2012; Otte & Spier, 2009).
Conclusion
The RAAS has a very important role in the maintenance of water and sodium balance, blood pressure, and vascular tone. It has been shown that its activity is present in renal and cardiac diseases and evaluations are going on to determine if it has a role in the dysfunction in other body organs. Aldosterone and renin ratios are being studied in dogs to help in the identification of primary hypoaldosteronism and primary hypoadrenocorticism. Future studies will be done to evaluate what roles RAAS has in conditions such as thyroid disease, hypertension, liver disease, and hypoadrenocorticism.
References
Carey, R. M. (2015). The intrarenal renin-angiotensin system in hypertension. Advances in chronic kidney disease, 22(3), 204-210.
Fountain, J. H., & Lappin, S. L. (2018). Physiology, Renin Angiotensin System. Treasure Island Florida, StatPearls Publishing.
Macia-Heras, M., Del Castillo-Rodriguez, N., & Navarro González, J. F. (2012). The renin-angiotensin-aldosterone system in renal and cardiovascular disease and the effects of its pharmacological blockade. J Diabetes Metab, 3(171), 2.
Otte, M., & Spier, A. (2009). The renin–angiotensin–aldosterone system: Approaches to cardiac and renal therapy. Compendium: Continuing Education for Veterinarians,, 31.
Weir, M. R., & Dzau, V. J. (1999). The renin-angiotensin-aldosterone system: a specific target for hypertension management. American journal of hyper