1)Beyond stimulating aldosterone secretion, list the effects of ANG II. Give exa
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1)Beyond stimulating aldosterone secretion, list the effects of ANG II. Give examples and brief descriptions of pharmaceutical agents that work by altering responses in the RAS pathway.
Angiotensin II (Ang II) increases blood pressure (BP) through several actions, such as vasoconstriction, sympathetic nerve stimulation, increased aldosterone biosynthesis, and renal action. Other Ang II actions include growth induction, cell migration, and mitosis in vascular smooth muscle cells, increased collagen types I and III synthesis in fibroblasts, and thickening and fibrosis of vessel walls and myocardium. Ang II is also involved in atherosclerosis and remodeling and repairing the myocardium after myocardial infarction. Finally, elevated Ang II is essential to neurohumoral activation in heart failure (F et al., 1995). The two major classes of drugs that target the RAS are angiotensin-converting enzyme (ACE) inhibitors and selective AT1 receptor blockers (ARBs). Although both of these drug classes target angiotensin II, the differences in their mechanisms of action have implications for their effects on other pathways and receptors that may have therapeutic implications. Both ACEIs and ARBs are effective antihypertensive agents that have been shown to reduce the risk of cardiovascular and renal events (Robles et al., 2013).
The kidneys assist in the regulation of blood pressure via the regulation of blood volume. How is renal regulation of blood volume achieved? Categorize your answers in terms of effects on GFR and reabsorption.
The glomerular filtration rate (GFR) is the amount of fluid filtered from the glomerular capillaries of the kidney into the Bowman’s capsule per unit of time. In addition to glomerular membrane permeability and surface area, it is determined by the balance of hydrostatic and colloidal osmotic pressure across the glomerular membrane. Renal blood flow moves from afferent arterioles to glomeruli, efferent arterioles, and peritubular capillaries. Filtration is the movement of fluid from plasma into Bowman’s capsule. Reabsorption is the movement of filtered substances from the tubules into the blood. Secretion is the movement of selected molecules from the blood into the tubules. The amount of solute excreted equals the amount filtered minus the amount reabsorbed and excreted. Between 80 and 180 mmHg of mean arterial blood pressure, autoregulation maintains renal blood flow so that GFR is constant. Decreased baroreceptor stimulation in response to hypotension and hypovolemia increases sympathetic input to the kidneys and circulatory system. Mediators such as catecholamines cause renal arteriolar constriction, further reducing renal blood flow and GFR to conserve blood volume (Silverthorn, 2019).
2)List the effects of ANG II.
Angiotensin II binds to several receptors throughout the body, affecting many different systems and functions. The effects of ANG II are increasing blood pressure by constricting blood vessels, triggering the sensation of thirst through the hypothalamus, and stimulating the release of ADH from the pituitary gland, which causes the kidneys to reabsorb water.
Give examples and brief descriptions of pharmaceutical agents that work by altering responses in the RAS pathway.
Blockade of the RAS with ACE inhibitors or angiotensin II type 1 receptor (AT1R) antagonists has become one of medicine’s most successful therapeutic approaches. RAS blockade decreases cardiovascular morbidity and mortality in patients with chronic heart failure or LV systolic dysfunction and after myocardial infarction. RAS blockers retard the progression of renal insufficiency in type 1 (ACE inhibitors) and type 2 (AT1R antagonists) diabetes mellitus and nondiabetic chronic renal disease.
How is renal regulation of blood volume achieved?
Autoregulation maintains renal blood flow between mean arterial blood pressures of 80 and 180 mmHg, so GFR is constant. Patients with mean arterial blood pressure below 80 mmHg will have decreased renal blood flow, GFR, and urine output. Furthermore, decreased baroreceptor stimulation, as occurs in response to hypotension and hypovolemia, will increase sympathetic input to the kidneys and circulating catecholamine and angiotensin production. These mediators cause renal arteriolar constriction, further decreasing renal blood flow and GFR to conserve blood volume.
