Atrial stretch

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

The most important stimulus to the release of ANP from the heart is atrial stretch via mechanosensitive ion channels. ANP release is also increased by volume expansion, changing from the standing to the supine position, and exercise. ANP release can also be increased by sympathetic stimulation via aiA-adrenoceptors, endothelins via the -receptor subtype (see below), glucocorticoids, and vasopressin. Plasma ANP concentration increases in various pathologic states, including heart failure, primary aldosteronism, chronic renal failure, and inappropriate ADH secretion syndrome. 

Guanylyl cyclase catalyses the reaction GTP — cGMP + pyrophosphate (PP ). Heart stress (e.g. atrial stretch due to increased blood pressure and hence increased cardiac muscle work)... 

Baroreceptors are present in the carotid sinus and aortic arch and stretch receptors are situated in the left atrium (G2, H6). Distension of the left atrium causes a fall in blood ADH levels, and in experimental animals the reduction in atrial stretch which follows the deflation of a distended balloon produces a brisk rise (S3). These experimental results offer an explanation of the dilutional situation with water retention which follows the surgical release of a tight mitral stenosis in man. 

It is generally accepted that the predominant mechanism of atrial fibrillation and atrial flutter is reentry. Atrial fibrillation appears to result from multiple atrial reentrant loops (or wavelets), and atrial flutter is due to a single, dominant reentrant substrate (counterclockwise circus movement around the tricuspid annulus). Atrial fibrillation or flutter usually occurs in association with forms of organic heart disease that causes atrial distension. Forms of heart disease that commonly lead to atrial stretch and precipitate atrial fibrillation or flutter include... 

Vasopressin (antidinretic hormone) is a nonapeptide that controls resorption of water by distal tubules of the kidney to regulate the osmotic pressure of blood. It functions to conserve body water by reducing the output of urine, and thus it is known as an antidiuretic. Vasopressin is synthesized in the supraoptic nucleus of the hypothalamus where it is bound to a neurophysin protein carrier, packaged in granules, and delivered by intracellular transport to nerve terminals in the posterior pituitary. Vasopressin bound to neurophysin is released from the granules in response to increased extracellular osmolarity sensed by hypothalamic osmoreceptors, signaling by atrial stretch receptors or after a rise in angiotensin n levels. Its secretion is increased by dehydration or stress and decreased after alcohol consumption. 

Vasopressin is released in response to increased extracellular osmo-larity sensed by hypothalamic osmoreceptors, signaling by atrial stretch receptors or after a rise in angiotensin II levels. Its secretion is increased by dehydration or stress. 

FIGURE 25 Atrial natriuretic factor (ANF) is a polypeptide hormone fliat is secreted mainly by flie heart atria in response to increases in atrial pressure or atrial stretch. 

The balance of sodium ion concentrations is governed by a number of mechanisms, including osmoreceptors in the hypothalamus and several volume receptors (e.g., intrathoracic, atrial stretch, and hepatic), and baroreceptors (e.g., intrarenal and arterial). These physiological mechanisms normally balance the plasma sodium and renal excretion of sodium, with approximately 80% of the sodium in the glomerular... 

Morton JB, Sanders P, Vohra JK, Sparks PB, Morgan JG, Spence SJ, Giigg LE, Kalman JM. Effect of chronic right atrial stretch on atrial electrical remodeling in patients with an atrial septal defect. Circulation. 2003 107 1775-1782. 

Nontraditional Hormones. Novel hormones identified ia cardiovascular tissue have profound effects on maintenance of blood pressure and blood volume ia mammals. Atrial natriuretic hormone (ANH) is a polypeptide hormone secreted from the atria of the heart. When the cardiac atrium is stretched by increased blood volume, secretion of ANH is stimulated ANH ia turn increases salt and water excretion and reduces blood pressure (6). Endothelin is a polypeptide hormone secreted by endothehal cells throughout the vasculature. Although endothelin is released into the circulation, it acts locally in a paracrine fashion to constrict adjacent vascular smooth muscle and increase blood pressure (7). 

Natriuretic Peptide Diuretics. Atrial natriuretic peptide (ANP), an endogenous diuretic, natriuretic, and vasodilator, is a peptide hormone primarily synthesized and stored by atrial cardiocytes, and secreted by the atria in response to mechanical stretch of the atria. It was discovered in the cmde extracts of atria in 1981 (51). ANP is also known as anaritide [95896-08-5] atrial natriuretic factor [104595-79-1] (ANF) auriculin ... 

Automaticity of cardiac fibers is controlled in part by activity of the sympathetic and parasympathetic nervous systems. Enhanced activity of the sympathetic nervous system may result in increased automaticity of the SA node or other automatic cardiac fibers. Enhanced activity of the parasympathetic nervous system tends to suppress automaticity conversely, inhibition of activity of the parasympathetic nervous system increases automaticity. Other factors may lead to abnormal increases in automaticity of extra-SA nodal tissues, including hypoxia, atrial or ventricular stretch [as might occur following long-standing hypertension or after the development of heart failure (HF)], and electrolyte abnormalities such as hypokalemia or hypomagnesemia. 

Atrial natriuretic peptide A type of peptide, 28 amino acids in length, secreted by the atria of the heart when atrial pressure and stretch are increased. 

Atrial natriuretic peptide (ANP) is produced by specialized myocytes in the atria of the heart. Secretion is stimulated by increased filling and stretch of the atria in response to plasma volume expansion. The effects of ANP include vasodilation, diuresis (increased urine production), and increased sodium excretion. Taken together, these effects decrease blood volume and blood pressure toward normal. 

In addition to its pump function, the heart is also a secretory organ. Cardiac cells produce two small peptides, the natriuretic factors, which oppose the vasoconstrictive actions of noradrenaline (norepinephrine) from the sympathetic nervous system and of the peptide angiotensin II. By causing vasodilation and natriuresis (increased excretion of sodium in the urine), atrial natriuretic peptide (ANP) secreted from the atria and B-type natriuretic peptide (BNP) secreted by both atria and probably more significantly, from the ventricles, reduce blood pressure. The stimulus to secretion of natriuretic peptides is wall stretch of the chambers of the heart, indicating volume and pressure overload of the vascular system. A third member of the natriuretic peptide family, CNP, is secreted by endothelial cells. 

ANP is a 28-amino-acid peptide first discovered by de Bold et al. (2). It is released from heart atrial myocytes in response to a local arterial wall stretch. ANP acts on outer adrenal cells to decrease aldosterone production and blood pressure, increase salt and water excretion, and transudate plasma water to the interstitium (3). 

The heart contains special receptors that respond to stretching. Activation of the stretch receptors results in the release of atrial natriuretic peptide (ANF) from the heart (Reis et ai 1997). The role of stretch in provoking AMP release was shown in the laboratory by inflating a balloon within the heart (Christensen and Leistad, 1997). ANP travels through the bloodstream to the kidneys, where it reduces the rate of sodium resorption. The result is a lowering of blood pressure and the appearance more salt in the urine (Lopez et ai., 1995). ANP i a 28-amino-acid polypeptide with the following sequence (Drewett and Garbers, 1994) ... 

Christensen, C., and Leistad, E. (1997), Atrial systolic piessute, as well as stretch, is a principal stimulus for release of ANE. Am. /. Pbpioi. 272, H820-HS26. 

Lavendustin A and derivatives have been used to study the pathophysiological role of protein kinases. For instance, lavendustin A was used to study the potential role of tyrosine kinases in the regulation of wall stretch-induced atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) secretion. Because lavendustin A is selective for t5n-osine kinases, the data obtained under these conditions showed that this kind of kinase is implicated in regulating cardiac hormone secretion. However, it is still unclear which tyrosine kinase is responsible for wall stretch-induced cardiac hormone secretion [111]. 

ATRIAL NATRIURETIC PEPTIDE RECEPTOR AGONISTS include ANP itself (also called atrial natriuretic factor (ANF), or atrlopeptin), a peptide made up of 28 amino acids and is contained in secretory granules in heart atrial cells. ANP is released in response to stretch in the atria, as occurs with increased central venous pressure, thus signalling volume overload in the circulation. The peptide has an effect on the kidney leading to increased Na and water excretion, vasodilation, increased vascular permeability and modified release of a number of other hormones and neurotransmitters. There are at least three related endogenous peptides ANP (atrial natriuretic peptide),... 

ANP and BNP are released in response to atrial and/or ventricular stretch from volume overload. Correspondingly,... 

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