Aldosterone
Aldosterone is a hormone produced by the adrenal glands that plays a key role in regulating blood pressure and electrolyte balance in the body. It acts on the kidneys to increase the reabsorption of sodium and water while promoting the excretion of potassium. This hormone is essential for maintaining proper fluid and electrolyte levels in the body.
7 Key excerpts on "Aldosterone"
eBook - ePub- Phillip A. Low, Phillip A. Low(Authors)
- 2011(Publication Date)
- Academic Press(Publisher)
...Aldosterone’s principal functions are to contain extracellular potassium (K) concentration within narrow limits and to maintain adequate extracellular volume by guarding against sodium (Na) loss. The two stimuli that regulate its secretion are therefore K (only small increments are required to significantly augment the levels of Aldosterone) and angiotensin II (which increases in response to the need for volume expansion and retention of additional Na). Although not as well-established, there is compelling evidence that the adrenergic nervous system influences Aldosterone secretion. Rays of adrenal medullary cells extending out to the zona glomerulosa have been described in the rat adrenal, and catecholamines have been shown to stimulate Aldosterone secretion in vitro. More recently, variants in the β-adrenergic receptor were found to associate with low renin hypertension. Taken together, the findings suggest the possibility of a significant contribution by the adrenergic nervous system to hypertensive states resulting from overproduction of Aldosterone [1]. Effects of Aldosterone That Target Distal Nephron The functions of Aldosterone begin with its occupancy of the nuclear receptor known as the mineralocorticoid receptor (MR). The ligand coupled to its receptor becomes a functioning transcription factor, and thus there is genomic delay in the onset of its actions. MR is expressed in a variety of tissues including the heart and brain, but the major site for its expression is the kidney’s distal nephron. Here, the principal target is the epithelial Na channel or ENaC located in cortical collecting duct [2]. Aldosterone induces translation for the protein serum glucocorticoid kinase type I (Sgk-1) [3]. The ultimate effect is to render an ubiquitin ligase (Nedd4-2) incapable of removing ENaC from the apical surface of the cell [4]...
eBook - ePub- Anthony W. Norman, Helen L. Henry(Authors)
- 2014(Publication Date)
- Academic Press(Publisher)
...The mineralocorticoids mediate their actions on ion balance principally in the kidney, and also to some limited extent in the salivary glands, gut, and sweat glands. In the kidney, the actions of the Aldosterone result in an increased cortical collecting tubule reabsorption of Na + with a concomitant secretion of K +. Only a fraction of the Na + filtered by the glomerulus is actually reabsorbed as a consequence of Aldosterone’s action. However, this fraction can effect significant consequences on electrolyte balance. The steroid hormone Aldosterone by binding to its nuclear receptor produces biological responses via stimulation of selected gene expression related to kidney tubule Na + transport. The focus of Aldosterone is on the mucosal cells of the kidney’s cortical collecting duct (see Figure 15-2). In the absence of Aldosterone, there is only a minimal basal uptake of Na + from the lumen (extracellular) side of the collecting duct cell by the Na + permease. Figure 15-5B illustrates the four steps in the cortical collecting duct cell which are operative in the presence of Aldosterone. The presence of Aldosterone binding to its nuclear receptor stimulates the gene transcription of several proteins that are essential to supporting the overall entrance of Na + into the cell via a Na + permease. Since the extracellular concentration of Na + is significantly higher (~140 mM) than the intracellular concentration of Na + (~10mM; see Table 15-3), the Na + in the cortical collecting duct cell’s cytosol must utilize the Na + /K-ATPase (see Figure 15-5B) to transfer the Na + across the peritubular cell membrane, against a concentration gradient, and release it into the extracellular fluid. E Atrial Natriuretic Protein System 1 Introduction The heart and brain are the source of a family of peptide hormones referred to as the atrial natriuretic peptide (ANP) system...
eBook - ePub- Anthony W. Norman, Gerald Litwack(Authors)
- 1997(Publication Date)
- Academic Press(Publisher)
...In addition, the growth factor properties of hormones are able to influence cardiovascular development and muscular hyperplasia or hypertrophy, as well as being involved with pathological changes that can be associated with atherosclerosis, cardiac hypertrophy, and heart failure. These hormone systems are also capable of mediating important biological effects in the kidney. The volume of the extracellular fluid (ECF) is governed by its Na + concentration. The Na + concentration of the ECF is determined by regulating the extent of excretion of Na + in the urine, which is mediated by Aldosterone and ANF. The principal, although not exclusive, factors governing the excretion of Na + are the steroid hormone Aldosterone and the glomerular filtration rate. The glomerular filtration of the kidney can be markedly increased by the actions of ANP, thus increasing the extraction of blood Na +. Also, ANP acts on the smooth muscle present in large arteries and vascular beds to effect relaxation and, thus, achieve a reduction in blood pressure. The function of Aldosterone is to directly stimulate the absorption of Na + by the renal tubules; this has the consequence of increasing the extracellular fluid volume. Thus, in the renin-angiotensin system, the rate of secretion of Aldosterone by the adrenal cortex is ultimately regulated by the extracellular fluid volume. As discussed in Chapter 10, bilateral adrenalectomy is fatal; this results from the absence of Aldosterone, which, in turn, leads to an increased loss of Na + in the urine, a concomitant retention of K + in the extracellular fluid, and loss of water from both the extracellular and intracellular compartments. If this process continues, death inevitably follows. B Renin-Angiotensin II Renin is an enzyme of 347 amino acids of molecular mass ≈42 kDa. Renin may be isolated from both kidney and mouse submaxillary glands...
eBook - ePubSteroid Biochemistry
Volume II
- R. Hobkirk(Author)
- 2018(Publication Date)
- CRC Press(Publisher)
...The renin-angiotensin system also seems to play an extremely important role; a decrease of the body sodium concentration stimulates this system to enhance the formation of Aldosterone synthesis at the adrenal zona glomerulosa level. Following this event, the Aldosterone formed acts at the kidney level to promote the excretion of potassium and the retention of sodium. From this, it can be seen that a very close interrelationship exists between the sodium ion that influences the synthesis of Aldosterone and the control by Aldosterone of the excretion of potassium and the retention of sodium. Recent studies have indicated that ACTH plays a more important role in the control of Aldosterone synthesis than was at first believed. There are also other factors such as prostaglandins, substances from the pineal gland and of neurohypophysial origin, that seem to contribute in the control of Aldosterone synthesis. Sites of action of control factors on the Aldosterone biosynthetic pathway are not completely known, and the mechanism of action of these substances at the molecular level is not understood. The study of the mode of action of control factors of Aldosterone synthesis is challenging and should contribute very interesting findings. ACKNOWLEDGMENT The author is grateful to the Medical Research Council of Canada, to Dr. D. Schapcott, and to Mrs. D. Tousignant. REFERENCES 1. Sandor, T., Fazekas, A. G., and Robinson, B. H., The biosynthesis of corticosteroids throughout the vertebrates, in General and Comparative Endocrinology of the Adrenal Cortex. Vol. 1, Chester Jones, I. and Henderson, I. W., Eds., Academic Press, London, 1976, chap. 2. 1a. Henderson, I. W., Chan, D. K. O., Sandor, T., and Chester Jones, I., The adrenal cortex and osmoregulation in telecosts, Mem. Soc. Endocrinol., 18, 31, 1970. 2. Greep, R. O. and Deane, H. W., The cytology and cytochemistry of the adrenal cortex, Ann. N. Y. Acad. Sci., 50, 596, 1949. 3. Myhre, E., Runt disease in rats, Acta Pathol...
eBook - ePub- Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner(Authors)
- 2017(Publication Date)
- CRC Press(Publisher)
...Therefore, it is crucial to recognize the syndrome, confirm the diagnosis, and provide a surgical cure to the appropriate individuals in order to prevent poor cardiovascular outcomes of hyperaldosteronism [ 2 ]. This chapter reviews the basics of physiology and epidemiology, describes important clinical features, summarizes diagnostic methods, and provides guidance in choosing an appropriate treatment option of PA [ 3 ]. PHYSIOLOGICAL MECHANISM OF Aldosterone SECRETION Control of Aldosterone secretion Aldosterone is a mineralocorticoid hormone, produced in the outer layer of the adrenal cortex (zona glomerulosa). Its main effects include sodium and fluid retention, via the exchange of potassium and hydrogen ions in the distal convoluted tubule of the kidney, resulting in increased intravascular volume (hypertension), hypokalemia, and metabolic alkalosis. A number of Aldosterone precursors, including deoxycorticosterone and 18-hydroxycorticosterone, have some mineralocorticoid activity, and their hypersecretion in various disorders may yield features of mineralocorticoid hypertension. Aldosterone participates in blood volume and serum potassium homeostasis; these physiologic parameters feed back to regulate Aldosterone secretion by the zona glomerulosa of the adrenal cortex [ 4 ]. Hypokalemia and hypervolemia suppress Aldosterone secretion, whereas blood volume depletion or an increase in serum potassium levels stimulates it. Aldosterone secretion is regulated mostly by the renin–angiotensin system and potassium levels, and minimally by adrenocorticotropic hormone (ACTH). In the case of PA, Aldosterone overproduction is independent of the juxtaglomerular apparatus and robust Aldosterone secretion suppresses production of renin. ACTH regulates Aldosterone secretion almost exclusively in the case of glucocorticoid-remediable aldosteronism (GRA), also known as FH type I (see also the “Familial Hyperaldosteronism Type I” section)...
eBook - ePubAdrenal Cortex
Butterworths International Medical Reviews: Clinical Endocrinology
- David C. Anderson, Jeremy S. D. Winter, David C. Anderson, Jeremy S. D. Winter(Authors)
- 2013(Publication Date)
- Butterworth-Heinemann(Publisher)
...In addition to these well-defined conditions, there are others in which mineralocorticoids are believed to play a role – albeit a poorly understood one. This review will deal with both, concentrating in the main on hypertension in man, and alluding only when necessary to animal models and experiments, on which so much of our current knowledge is based. Table 8.1 Hypertension associated with known mineralocorticoids Disease Lesion Steroid involved Primary aldosteronism Conn’s syndrome Adrenal adenoma Aldosterone (+ other steroids?) Idiopathic aldosteronism Bilateral hyperplasia of the zona glomerulosa Aldosterone (+ other steroids?) Dexamethasone suppressible aldosteronism Bilateral hyperplasia of the zona glomerulosa Aldosterone (+ other steroids?) Cushing’s syndrome Hypothalamic and/or pituitary dysfunction (DOC, cortisol, corticosterone) Adrenal adenoma Adrenal carcinoma Ectopic production of ACTH Congenital adrenal hyperplasia Enzymic defect Biglieri’s syndrome 17α-Hydroxylase DOC, 18-OH DOC New’s syndrome 11β-Hydroxylase DOC, deoxycortisol DOC = deoxycorticosterone. Poiseuille’s law of fluid dynamics tells us that pressure results from the effects of both flow and resistance. Translated into physiological terms and applied to the cardiovascular system, this means that blood pressure is proportional to cardiac output and peripheral resistance, both of which depend on several physiological parameters (Guyton et al., 1974). Cardiac output depends on heart rate, systolic ejection volume and blood volume, while vascular resistance depends on arteriolar sensitivity and reactivity to vasoactive humoral agents and neurogenic factors, and on wall thickness and compliance. Since mineralocorticoids by definition retain sodium chloride followed by water, and thereby increase blood volume, it was believed at first that they acted on the cardiovascular system via changes in blood volume...
- I. Chester Jones, I. W. Henderson, I. Chester Jones, I. W. Henderson(Authors)
- 2013(Publication Date)
- Academic Press(Publisher)
...It appears to be limited to the kidney. Other epithelia influenced by Aldosterone, such as those of the gut, salivary and sweat glands, do not show escape. The rise in blood pressure appears to be dependent on a changed sodium metabolism and does not occur if a low sodium diet is given during the period of administration of the steroid (Gross et al., 1957 ; Brown et al., 1971). Moreover, it is the sodium-retaining rather than the potassium-losing action which escapes and, consequently, serum potassium concentration falls. Urinary potassium excretion rate balances intake but is inappropriately high for the serum level. An otherwise normal individual who develops some condition, for example an adrenal tumour, in which there is excessive production of Aldosterone or other mineralocorticoids will, when first seen, be in a state similar to that of one who has been given Aldosterone for a long period and has developed renal escape. Fig. 2 Effects of a mineralocorticoid, 9-α-fluorocortisol, in a normal individual on bowel electrical activity (colonie electrical p.d. (mV)), serum and urinary electrolytes, body weight and blood pressure. Note that “renal” escape occurred after six days, but there was persistent elevation of the bowel transepithelial electrical potential difference indicating continuing stimulation of the sodium transport system. On the other hand, the pathophysiological effects of Aldosterone are very different if escape does not take place (Fig. 3). For then, sodium retention continues and fluid is also retained. Oedema and ascites eventually occur but hypertension and a disturbed potassium metabolism are inconspicuous. The latter is probably because, in the absence of escape, there is a continued increased sodium reabsorption in the renal tubules proximal to the region of potassium secretion...
