Renin-angiotensin-aldosterone mechanism

The compensatory responses to hydralazine use are tachycardia and salt and water retention. These responses are generated by the baroreceptor and renin-angiotensin-aldosterone mechanisms summarized in Figure 6-4. The motor limb of the sympathetic response consists of outflow from the vasomotor center to the heart and vessels, as shown in Figure 11-3. You should be able to reproduce these diagrams from memory. 

The renin-angiotensin-aldosterone mechanism also responds to changes in fluid volume ... 

The low fluid volume triggers the renin-angiotensin-aldosterone mechanism. 

When the temporal sequence of adjustments of blood pressure is analysed it seems, that CNS mechanisms (e.g., baroreflexes) will provide regulation of the circulation within seconds to minutes. Other mechanisms, such as the renin-angiotensin-aldosterone system and fluid shifts, occur over minutes to hours. Only the... 

Assuming the capsular pressures opposing the movement of water out of the blood and into the top of the nephron are constant, the net filtration pressure is due largely to the blood pressure. Any fall in blood pressure can have a dramatic effect on the efficiency of filtration and therefore clearance of waste materials. So important is the pressure within the renal vasculature that the kidney is critical in regulating systemic blood pressure via the renin-angiotensin-aldosterone (RAA) axis, a physiological process which relies on transport mechanisms within the renal tubules. 

Mechanism of Action An ACE inhibitor that suppresses the renin-angiotensin-aldosterone system. Decreases plasma angiotensin II, increases plasma renin activity, and decreases aldosterone secretion. Therapeutic Effect Reduces peripheral arterial resistance and BP. 

Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11-1) arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of vasoactive substances from vascular endothelium may also be involved in the regulation of vascular resistance. For example, endothelin-1 (see Chapter 17) constricts and nitric oxide (see Chapter 19) dilates blood vessels. 

Neurohumoral (extrinsic) compensation involves two major mechanisms (previously presented in Figure 6-7)—the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal response—plus several others. Some of the pathologic as well as beneficial features of these compensatory responses are illustrated in Figure 13-2. The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure, in patients with heart failure. As a result, baroreceptor sensory input to the vasomotor center is reduced even at normal pressures sympathetic outflow is increased, and parasympathetic outflow is decreased. Increased sympathetic outflow causes tachycardia, increased cardiac contractility, and increased vascular tone. Vascular tone is further increased by angiotensin II and endothelin, a potent vasoconstrictor released by vascular endothelial cells. The result is a vicious cycle that is characteristic of heart failure (Figure 13-3). Vasoconstriction increases afterload, which further reduces ejection fraction and cardiac output. Neurohumoral antagonists and vasodilators... 

Normally, the activity of the renin-angiotensin-aldosterone system is kept in balance by its own feedback mechanisms. Liver diseases have a lasting impact on this regulatory system by changing the formation and breakdown of the substances involved. The main stimuli of the RAAS are hypovolaemia, hypotension, hypoxia,... 

Bernard , M., Trevisani, R, Gasbarrini, G. Mechanisms involved in ascites formation renin-angiotensin-aldosterone system. Gastroenterol. Internal. 1992 5 237-241... 

Many factors contribute to ventricular remodehng, including neurohormonal factors (e.g., activation of the renin-angiotensin-aldosterone and sympathetic nervous systems), hemodynamic factors, mechanical factors, and changes in gene expression. This process affects both cardiomyocytes (cardiomyocyte hypertrophy, loss of cardiomyocytes) and the extracellular matrix (increased interstitial fibrosis), thereby promoting both systohc and diastohc dysfunction. ... 

Diuretics are drugs that increase the rate of urine flow clinically useful diuretics also increase the rate of excretion of Na+ (natiiuresis) and an accompanying anion, usually CD. Most clinical applications of diuretics aim to reduce extracellular fluid volume by decreasing total-body NaCl content. Although continued administration of a diuretic causes a sustained net deficit in total-body Na+, the time course of natriuresis is finite because renal compensatory mechanisms bring Na+ excretion in line with Na+ intake, a phenomenon known as diuretic braking. Compensatory mechanisms include activation of the sympathetic nervous system, activation of the renin-angiotensin-aldosterone axis, decreased arterial blood pressure (which reduces pressure natriuresis), hypertrophy of renal epithelial cells, increased expression of renal epithelial transporters, and perhaps alterations in natriuretic hormones such as atrial natriuretic peptide. 

EFFECTS ON URINARY EXCRETION Loop diuretics profoundly increase the urinary excretion of Na+ and Cl" (i.e., up to 25% of the filtered load of Na+) and markedly increase the excretion of Ca + and Mg +. Furosemide but not bumetanide also has weak carbonic anhydrase-inhibiting activity that increases the urinary excretion of HCO " and phosphate. AU inhibitors of the Na+-K+-2CL symporter increase the urinary excretion of K+ and titratable acid, due in part to increased delivery of Na+ to the distal tubule. The mechanism by which increased distal delivery of Na+ enhances excretion of K+ and H+ is discussed in the section on inhibitors of Na+ channels. Other mechanisms contributing to enhanced K+ and H+ excretion include flow-dependent enhancement of ion secretion by the collecting duct, nonosmotic vasopressin release, and activation of the renin-angiotensin-aldosterone axis. Loop diuretics acutely increase the excretion of uric acid, whereas their chronic administration reduces uric acid excretion, possibly due to enhanced transport in the proximal tubule secondary to volume depletion or to competition between the diuretic and uric acid for the organic acid secretory mechanism in the proximal tubule. 

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