PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 14737833

[Aldosterone].

Isamu Miyamori
View original source ↗Export metadata ↓

Abstract

Nonepithelial effect of aldosterone has been recognized as a cardiovascular risk factor independent of elevation of blood pressure. Pro-inflammatory effect of aldosterone in vasculature appears to be an initiating event for the target organ injuries. Recent clinical trials of aldosterone receptor blockers in congestive heart failure indicate the efficacy of aldosterone antagonism to prevent cardiac death. In addition to elevated plasma levels of aldosterone, mineralocorticoid receptor expression in cardiovascular tissues may contribute to the progression of heart failure. In this review, emerging role of aldosterone as a cardiovascular risk is highlighted.

Explore related subjects

AldosteroneAnimalsHeart FailureHumansReceptors, MineralocorticoidEnglish AbstractJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Isamu Miyamori. 2004. [Aldosterone].. https://pubmed.ncbi.nlm.nih.gov/14737833/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Spironolactone preserves cardiac norepinephrine reuptake in salt-sensitive Dahl rats.

An impairment of cardiac norepinephrine (NE) reuptake via the neuronal NE transporter (NET) enhances the effects of increased cardiac NE release in heart failure patients. Increasing evidence suggests that aldosterone and endothelins promote sympathetic overstimulation of failing hearts. Salt-sensitive Dahl rats (DS) fed a high-salt diet developed arterial hypertension and diastolic heart failure as well as elevated plasma levels of endothelin-1 and NE. Cardiac NE reuptake and NET-binding sites, as assessed by clearance of bolus-injected [(3)H]NE in isolated perfused rat hearts and [(3)H]mazindol binding, were reduced. Treatment of DS with the mineralocorticoid receptor antagonist spironolactone preserved the plasma levels of endothelin-1 and NE, cardiac NE reuptake, and myocardial NET density. Moreover, the ventricular function and survival of spironolactone-treated DS were significantly improved compared with untreated DS. The alpha(1)-inhibitor prazosin decreased blood pressure in DS similar to spironolactone treatment, but did not normalize the plasma levels of endothelin-1 and NE, NE reuptake, or ventricular function. In a heart failure-independent model, Wistar rats that were infused with aldosterone and fed a high-salt diet developed impaired cardiac NE reuptake. Treatment of these rats with the endothelin A receptor antagonist darusentan attenuated the impairment of NE reuptake. In conclusion, spironolactone preserves NET-dependent cardiac NE reuptake in salt-dependent heart failure. Evidence is provided that aldosterone inhibits NET function through an interaction with the endothelin system. Selective antagonism of the mineralocorticoid and/or the endothelin A receptor might represent therapeutic principles to prevent cardiac sympathetic overactivity in salt-dependent heart failure.

Aldosterone↗
PubMed2006

Hypokalemia in a mouse model of Gitelman's syndrome.

Hypokalemia is a prominent feature of Gitelman syndrome and a common side effect of thiazide use in the treatment of hypertension. It is widely recognized that genetic or pharmacological inhibition of the renal thiazide-sensitive sodium-chloride cotransporter (NCC) initiates the potentially severe renal potassium loss observed in these settings. Surprisingly, hypokalemia has not been detected in NCC (-/-) mice maintained on normal rodent diets (Schultheis PJ, Lorenz JN, Meneton P, Nieman ML, Riddle TM, Flagella M, Duffy JJ, Doetschman T, Miller ML, and Shull GE. J Biol Chem 273: 29150-29155, 1998). We show that modest reduction of dietary potassium induced a marked reduction in plasma potassium and elevated renal potassium excretion in NCC (-/-) mice that was associated with a pronounced polydipsia and polyuria of central origin. These findings are consistent with the development of potassium depletion in NCC (-/-) mice and were not seen in wild-type mice maintained on the same low-potassium diet. In addition, plasma aldosterone levels were significantly elevated in NCC (-/-) mice even in the presence of a low-potassium diet. Collectively, these findings suggest an early central component to the polyuria of Gitelman syndrome and show that both elevated aldosterone and dietary potassium content contribute to the development of hypokalemia in Gitelman syndrome. Therefore, NCC (-/-) mice are more sensitive to reductions in dietary potassium than wild-type mice and become hypokalemic, thus more faithfully representing the Gitelman phenotype seen in humans.

Aldosterone↗
PubMed2006

Lack of effect of metyrapone and exogenous cortisol on early porcine conceptus development.

A study was conducted to evaluate the influence of maternal cortisol on early conceptus development in pigs (Sus scrofa). The corticosteroid synthesis inhibitor metyrapone was injected daily during days 14-19 of pregnancy, without (n = 6) and with commensurate administration of cortisol (n = 6). Blood samples were taken via an indwelling jugular catheter on days 14 and 18, and conceptuses were harvested during surgery on day 20. Compared with vehicle-injected control dams (n = 7) plasma cortisol and aldosterone concentrations were decreased (P < 0.01) by 52 and 29%, respectively, by metyrapone treatment. Cortisol administration reversed decreases in plasma cortisol by day 18. There were no treatment-associated effects on conceptus survival or size. Nor were there treatment-associated effects on allantoic fluid volume or content. Trophodermal glucocorticoid receptor (GR) mRNA expression decreased by 34% (P < 0.05) in metyrapone-treated pigs, and was not further influenced by concomitant administration of cortisol, thereby suggesting an influence of aldosterone on GR mRNA expression. Also, when all pigs were considered, there were treatment-independent second-order polynomial regressions (P < 0.05) between maternal plasma cortisol concentrations and embryonic weight, allantoic size and allantoic glucose concentrations, and between plasma aldosterone concentrations and trophodermal GR mRNA expression. Such biphasic corticosteroid concentration versus tissue parameter curves are noteworthy, but difficult to interpret validly. They may suggest that an appropriate corticosteroid environment is necessary for optimal porcine embryonic development during this stage of gestation, but cannot overshadow the absence of treatment effects on the porcine embryonic measures evaluated.

Aldosterone↗