Thus, increased production and action of ANG II specifically in the subfornical organ are sufficient on their own to mediate an increase in drinking through PKC. Keywords: Cre-recombinase; adenovirus; brain; renin-angiotensin system; subfornical organ. Abstract Increased activity of the renin-angiotensin system within the brain elevates fluid intake, blood pressure, and resting metabolic rate. This increases the arterial pressure of the patient. Angiotensin II also acts on the adrenal cortex, specifically the zona glomerulosa.
Here, it stimulates the release of aldosterone. Aldosterone is a steroid hormone that causes an increase in sodium reabsorption and potassium excretion at the distal tubule and collecting duct of the nephron. The net effect is an increased level of sodium reabsorption. This has the same effect as mentioned previously: the increased total body sodium leads to an increase in osmolarity and subsequent increase in blood and ECF volume. In contrast to angiotensin II, aldosterone is a steroid hormone.
As a result, it enacts change by binding to nuclear receptors and altering gene transcription. Thus, the effects of aldosterone may take hours to days to begin, while the effects of angiotensin II are rapid. The effect of angiotensin II on vasoconstriction takes place in systemic arterioles. Here, angiotensin II binds to G protein-coupled receptors, leading to a secondary messenger cascade that results in potent arteriolar vasoconstriction.
This acts to increase total peripheral resistance, causing an increase in blood pressure. Finally, angiotensin II acts on the brain. Here, it has three effects. First, it binds to the hypothalamus, stimulating thirst and increased water intake. Second, it stimulates the release of antidiuretic hormone ADH by the posterior pituitary.
ADH, or vasopressin, acts to increase water reabsorption in the kidney by inserting aquaporin channels at the collecting duct. Finally, angiotensin II decreases the sensitivity of the baroreceptor reflex. This diminishes baroreceptor response to an increase in blood pressure, which would be counterproductive to the goal of the RAAS. The net effect of these interactions is an increase in total body sodium, total body water, and vascular tone. The RAAS acts to manage blood volume and arteriolar tone on a long-term basis.
While minor and rapid shifts are typically managed via the baroreceptor reflex, the RAAS can alter blood volume chronically. Though the RAAS serves a critical function, it can be activated inappropriately in several conditions that may then lead to the development of hypertension.
For example, renal artery stenosis results in a decreased volume of blood reaching one or both kidneys. As a result, the juxtaglomerular cells will sense a decrease in blood volume, activating the RAAS. This can lead to an inappropriate elevation of circulating blood volume and arteriolar tone due to poor renal perfusion. Pharmacologically, the RAAS is a frequently manipulated system in the management of heart failure, hypertension, diabetes mellitus, and acute myocardial infarction.
ACE inhibitors e. The varied mechanisms of these drugs allow their utilization in different scenarios. ACE inhibitors inhibit the action of angiotensin-converting enzymes, thus decreasing the production of angiotensin II. Aldosterone inhibitors have two specific varieties. The first e. These work by preventing the binding of aldosterone to binding sites in the kidney, preventing insertion of Na channels.
The second e. In these cases, blocking or decreasing levels of angiotensin II will lead to a reduction in blood pressure. The implication that these population data demonstrating a small but statistically significant relationship of PRA with outcome can be used as a guide to treatment of individuals with a similar disease is highly suspect. Hazard ratios of 1. Furthermore, nothing in the data leads us to conclude that RAS inhibitors would counteract the apparent adverse influence of PRA on outcome.
Despite copious data from well-designed large-scale trials we still do not know how to use measures of RAS activity to help steer management of cardiovascular diseases. Google Scholar. Oxford University Press is a department of the University of Oxford.
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Volume Article Contents References. Is activation of the renin—angiotensin system hazardous to your health? Cohn Jay N. Oxford Academic. Cite Cite Jay N. Select Format Select format. Permissions Icon Permissions. Figure 1. Open in new tab Download slide. Google Scholar Crossref. Search ADS. The renin system: variations in man measured by radioimmunoassay and bio-assay. Renin profiling for diagnosis, risk assessment and treatment of hypertension.
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Structural basis for heart failure: ventricular remodeling and its pharmacological inhibition.
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