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Chemical Compound Review

ALDOSTERONE     (8S,9R,10R,11S,13R,14S,17S)- 11-hydroxy-17...

Synonyms: Aldocorten, Aldocortin, Aldocortene, Aldosterona, Aldosteronum, ...
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Disease relevance of ALDOSTERONE

  • The objective of this study was to produce hypertension in rats by chronic infusion of d-aldosterone, a more potent mineralocorticoid [1].
  • Four patients with EH and 2 AI normotensive patients had elevated ALD/PRA ratios but normal responses to the suppressive tests, thus excluding diagnosis of primary aldosteronism [2].
  • The prolonged infusion with SRIF-A alone caused, in sham-operated rats, a marked increase in PAC and a significant hypertrophy of ZG and ZG cells; basal and maximally-stimulated ALDO secretion of dispersed ZG cells was also notably raised [3].
  • 2. Animals received D-aldosterone or dexamethasone (10 microgram/100 g body weight) daily for 3 days [4].
  • Administering D-aldosterone, 7 microgram 100 g-1, to rats results in a marked rise in ammonium excretion and metabolic alkalosis [5].
  • Urinary aldosterone excretion and AngII-stimulated aldosterone are increased in overweight, compared with lean, normotensive adults [6].
  • There is evidence that a long-term increase in aldosterone production from early life is determined by an interaction of genetic and environmental factors, leading to the eventual phenotypes of aldosterone-associated hypertension and cardiovascular damage in middle age and beyond [7].
  • The low doses of the fadrozole enantiomers did not change cardiac fibrosis or plasma aldosterone but similarly reduced urinary aldosterone excretion rate [8].
  • Of them 999 had primary (essential) hypertension (PH) and 126 (11.2%) PA caused by an aldosterone-producing adenoma in 54 (4.8%) [9].

High impact information on ALDOSTERONE

  • At a dose of 16 mg/day, CGS 16949A produced significant (P less than 0.001) suppression of both basal and ACTH-stimulated ALDO production [10].
  • The influx of 22Na into the smooth muscle cells of incubated rat tail arteries was measured directly, in the presence and absence of 2.8 X 10(-7) M D-aldosterone [11].
  • In contrast, in control children, PRA was suppressed, while Aldo increased, resulting in a fall of the PRA to pH 1 Aldo ratio [12].
  • The PRA to pH 1 Aldo ratio remained normal with normal and low Na+ diets, regardless of DEX administration, indicating normal glomerulosa function with renin stimulation [12].
  • Chronic infusion of d-aldosterone into uninephrectomized rats on high sodium intake resulted in a significant increase in systolic blood pressure [13].

Chemical compound and disease context of ALDOSTERONE

  • Upright ALD and PRA determination was performed in all cases while patients with abnormal ALD/PRA ratios were submitted to confirmatory tests (saline infusion and captopril tests) for diagnosis of primary aldosteronism [2].

Biological context of ALDOSTERONE

  • Seven chronically catheterized fetal lambs between 100 and 130 days gestation (term, 140 to 145 days) and five unborn lambs were infused with d-aldosterone monoacetate, 100 microgram/kg bolus, and 100 microgram/kg over 60 min [14].
  • Thus the expression of the ANG gene in the studied areas of rat forebrain is predominantly under the control of the adrenal glucocorticoids via the type II receptor and not regulated by an ALDO dose that stabilizes natriuresis from the kidney [15].
  • These results indicate that ET-induced NO formation might mitigate increases in venous as well as arterial vascular resistance and changes in renal handling of water and electrolytes, and might also play an inhibitory role in ANP release but not in PRA or AVP and ALD release [16].
  • Urinary parameters related to acid base homeostasis were studied in adrenalectomized rats (ADX) as well as in ADX treated with physiological doses of corticosterone (B), aldosterone (aldo) or 18-Hydroxycorticosterone (18HOB) during 1, 3 or 5 days, under basal conditions and after gravage with 200 mM HCI [17].
  • During hibernation of tortoises, a marked decrease in the short-circuit current together with an increase in the electrical resistance are observed across the small intestine, colon and bladder mucosa and D-aldosterone (which is decreased in the plasma) has no effect on these parameters [18].

Anatomical context of ALDOSTERONE


Associations of ALDOSTERONE with other chemical compounds


Gene context of ALDOSTERONE

  • Although the twofold increment in ALDO with exercise remained intact during the INDO trial, the PRA response to exercise was significantly blunted [28].
  • Isolated ZG cells and autotransplant slices from SRIF-infused rats evidenced a notable decrease in both their basal and maximally ACTH- or ANG-II-stimulated ALDO production [3].
  • DOC responses to ACTH in the adrenal vein effluents correlated significantly with Aldo responses but not with the 17-OHP increments, suggesting that the adrenal responses of Aldo and DOC to ACTH are events that probably occur in the same zone [29].
  • The enhancement in ornithine decarboxylase activity produced by d-aldosterone was maximal at 3 h after the injection of the hormone [30].
  • 4. D-Aldosterone had no significant effect on kallikrein release, either in urine or in venous outflow [4].
  • Although blood pressure and cardiac structure were unchanged in this young study population, our findings indicate a new link between MDR1 genotype and the aldosterone system in humans [31].
  • Most importantly, we demonstrated that aldosterone also increases elastin mRNA levels, tropoelastin synthesis, and elastic fiber deposition in a dose-dependent manner [32].
  • Dominant-negative Rac1 also inhibited aldosterone-induced ACE gene expression [33].

Analytical, diagnostic and therapeutic context of ALDOSTERONE

  • OPC-31260 also increased water metabolism and sodium excretion and reduced urinary ALD, although the aquaretic effect was only evident during the first 2 days, and no effects on serum osmolality, renal filtration, and systemic hemodynamics were observed [34].
  • Isolated ZG cells and autotransplant quarters obtained from VIP-infused rats evidenced a notable increase in both their basal and maximally ACTH- or ANG-II-stimulated ALDO secretion [35].
  • METHODS: ALD and PRA were measured by specific radioimmunoassays [2].
  • 3. Intraperitoneal injections of D-aldosterone caused a slight reduction of transmural potential difference (PD) and short-circuit current (Isc) [36].


  1. Aldosterone infusion into the rat and dose-dependent changes in blood pressure and arterial ionic transport. Garwitz, E.T., Jones, A.W. Hypertension (1982) [Pubmed]
  2. Primary aldosteronism in normokalemic patients with adrenal incidentalomas. Bernini, G., Moretti, A., Argenio, G., Salvetti, A. Eur. J. Endocrinol. (2002) [Pubmed]
  3. Evidence that endogenous somatostatin (SRIF) exerts an inhibitory control on the function and growth of rat adrenal zona glomerulosa. The possible involvement of zona medullaris as a source of endogenous SRIF. Rebuffat, P., Belloni, A.S., Musajo, F.G., Rocco, S., Markowska, A., Mazzocchi, G., Nussdorfer, G.G. J. Steroid Biochem. Mol. Biol. (1994) [Pubmed]
  4. Dexamethasone, aldosterone and kallikrein release by isolated rat kidney. Vio, C.P., Roblero, J.S., Croxatto, H.R. Clin. Sci. (1981) [Pubmed]
  5. Influence of aldosterone on renal ammonia production. Welbourne, T.C., Francoeur, D. Am. J. Physiol. (1977) [Pubmed]
  6. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet. Bentley-Lewis, R., Adler, G.K., Perlstein, T., Seely, E.W., Hopkins, P.N., Williams, G.H., Garg, R. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  7. A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function. Connell, J.M., MacKenzie, S.M., Freel, E.M., Fraser, R., Davies, E. Endocr. Rev. (2008) [Pubmed]
  8. Fadrozole reverses cardiac fibrosis in spontaneously hypertensive heart failure rats: discordant enantioselectivity versus reduction of plasma aldosterone. Minnaard-Huiban, M., Emmen, J.M., Roumen, L., Beugels, I.P., Cohuet, G.M., van Essen, H., Ruijters, E., Pieterse, K., Hilbers, P.A., Ottenheijm, H.C., Plate, R., de Gooyer, M.E., Smits, J.F., Hermans, J.J. Endocrinology (2008) [Pubmed]
  9. Body mass index predicts plasma aldosterone concentrations in overweight-obese primary hypertensive patients. Rossi, G.P., Belfiore, A., Bernini, G., Fabris, B., Caridi, G., Ferri, C., Giacchetti, G., Letizia, C., Maccario, M., Mannelli, M., Palumbo, G., Patalano, A., Rizzoni, D., Rossi, E., Pessina, A.C., Mantero, F. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  10. The effects of CGS 16949A, an aromatase inhibitor on adrenal mineralocorticoid biosynthesis. Demers, L.M., Melby, J.C., Wilson, T.E., Lipton, A., Harvey, H.A., Santen, R.J. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  11. Direct measurement of sodium influx in vascular smooth muscle. Stimulation by aldosterone. Menard, M.R., Friedman, S.M. Hypertension (1985) [Pubmed]
  12. Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function. Pang, S., Levine, L.S., Stoner, E., Opitz, J.M., Pollack, M.S., Dupont, B., New, M.I. J. Clin. Endocrinol. Metab. (1983) [Pubmed]
  13. Altered chloride transport in arteries from aldosterone salt-hypertensive rats. McMahon, E.G., Jones, A.W. J. Hypertens. (1988) [Pubmed]
  14. Transplacental transfer of aldosterone and its effects on renal function in the fetal lamb. Siegel, S.R., Oakes, G., Palmer, S. Pediatr. Res. (1981) [Pubmed]
  15. Regulation of angiotensinogen gene expression in the rat forebrain by adrenal steroids and relation to salt appetite. Riftina, F., Angulo, J., Pompei, P., McEwen, B. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  16. Effects of endothelin-induced nitric oxide on venous circulation and renal water-electrolyte handling. Ota, K., Kimura, T., Shoji, M., Ota, M., Funyu, T., Mori, T., Sahata, T. J. Cardiovasc. Pharmacol. (1998) [Pubmed]
  17. Effects of chronic treatments with adrenal steroids on acid-base homeostasis in the rat. Igarreta, M.P., Lantos, C.P., Damasco, M.C. Acta physiologica, pharmacologica et therapeutica latinoamericana : órgano de la Asociación Latinoamericana de Ciencias Fisiológicas y [de] la Asociación Latinoamericana de Farmacología. (1996) [Pubmed]
  18. Seasonal changes in the electrical parameters of the small intestine, colon and bladder mucosa of land tortoises (testudo hermanni hermanni Gmelin). Gilles-Baillien, M., Verbert, M. Experientia (1978) [Pubmed]
  19. Effects of adrenal steroid manipulations and repeated restraint stress on dynorphin mRNA levels and excitatory amino acid receptor binding in hippocampus. Watanabe, Y., Weiland, N.G., McEwen, B.S. Brain Res. (1995) [Pubmed]
  20. Direct stimulation of human erythrocyte membrane (Na+ + k+)-mg ATPase activity in vitro by physiological concentrations of d-aldosterone. Hamlyn, J.M., Duffy, T. Biochem. Biophys. Res. Commun. (1978) [Pubmed]
  21. Central effects of aldosterone infused into the rat subcommissural organ region. Dundore, R.L., Wurpel, J.N., Balaban, C.D., Keil, L.C., Severs, W.B. Neurosci. Res. (1984) [Pubmed]
  22. Effects of angiotensin II and aldosterone on diastolic function in vivo in normal man. Clarkson, P.B., Wheeldon, N.M., MacLeod, C., Tennent, M., MacDonald, T.M. Clin. Sci. (1994) [Pubmed]
  23. Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt-induced hypertension. Bayorh, M.A., Ganafa, A.A., Eatman, D., Walton, M., Feuerstein, G.Z. Am. J. Hypertens. (2005) [Pubmed]
  24. Modulation of angiotensin II binding sites in neuronal cultures by mineralocorticoids. Sumners, C., Fregly, M.J. Am. J. Physiol. (1989) [Pubmed]
  25. Relationship between aldosterone and progesterone in the human menstrual cycle. Szmuilowicz, E.D., Adler, G.K., Williams, J.S., Green, D.E., Yao, T.M., Hopkins, P.N., Seely, E.W. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  26. The role of polyester interstitium and aldosterone during structural development of renal tubules in serum-free medium. Minuth, W.W., Denk, L., Hu, K. Biomaterials (2007) [Pubmed]
  27. Aldosterone increases oxidant stress to impair guanylyl cyclase activity by cysteinyl thiol oxidation in vascular smooth muscle cells. Maron, B.A., Zhang, Y.Y., Handy, D.E., Beuve, A., Tang, S.S., Loscalzo, J., Leopold, J.A. J. Biol. Chem. (2009) [Pubmed]
  28. Exercise-induced proteinuria is attenuated by indomethacin. Mittleman, K.D., Zambraski, E.J. Medicine and science in sports and exercise. (1992) [Pubmed]
  29. Suppression and stimulation of mineralocorticoid hormones (MCH) in the simple virilizing form of congenital adrenal hyperplasia (CAH) evaluated by the quantitation in adrenal venous blood. Wajchenberg, B.L., Biglieri, E.G., Okada, H., Malerbi, D.A., Achando, S.S., Kater, C.E. J. Steroid Biochem. (1983) [Pubmed]
  30. In vivo hormonal induction of ornithine decarboxylase in rat kidney. Scalabrino, G., Ferioli, M.E. Endocrinology (1976) [Pubmed]
  31. MDR1 genotype-dependent regulation of the aldosterone system in humans. Zolk, O., Jacobi, J., Pahl, A., Fromm, M.F., Schmieder, R.E. Pharmacogenet. Genomics (2007) [Pubmed]
  32. Aldosterone induces elastin production in cardiac fibroblasts through activation of insulin-like growth factor-I receptors in a mineralocorticoid receptor-independent manner. Bunda, S., Liu, P., Wang, Y., Liu, K., Hinek, A. Am. J. Pathol. (2007) [Pubmed]
  33. Aldosterone induces superoxide generation via Rac1 activation in endothelial cells. Iwashima, F., Yoshimoto, T., Minami, I., Sakurada, M., Hirono, Y., Hirata, Y. Endocrinology (2008) [Pubmed]
  34. Comparison of two aquaretic drugs (niravoline and OPC-31260) in cirrhotic rats with ascites and water retention. Bosch-Marcé, M., Poo, J.L., Jiménez, W., Bordas, N., Leivas, A., Morales-Ruiz, M., Muñoz, R.M., Pérez, M., Arroyo, V., Rivera, F., Rodés, J. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  35. Evidence that endogenous vasoactive intestinal peptide (VIP) plays a role in the maintenance of the growth and steroidogenic capacity of rat adrenal zona glomerulosa. Rebuffat, P., Nowak, K.W., Tortorella, C., Musajo, F.G., Gottardo, G., Mazzocchi, G., Nussdorfer, G.G. J. Steroid Biochem. Mol. Biol. (1994) [Pubmed]
  36. The role of aldosterone in water and electrolyte transport across the colonic epithelium of the lizard, Gallotia galloti. Diaz, M., Lorenzo, A., Badia, P., Gomez, T. Comparative biochemistry and physiology. A, Comparative physiology. (1988) [Pubmed]
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