1,721,195 research outputs found
Corticosteroid receptors in lymphocytes: a possible marker of brain involution?
No full textA similarity has recently been found between the regulation of corticosteroid receptors in brain and in lymphoid tissue. We have studied the regulation of corticosteroid receptors in human mononuclear leukocytes as a possible marker of brain involution. Type I corticosteroid receptors are down regulated by excess of mineralocorticoids (primary and secondary hyperaldosteronism, pseudohyperaldosteronism) and of glucocorticoids (Cushing's syndrome). Type II corticosteroid receptors are not reduced by excess of endogenous corticosteroids (Cushing's syndrome). In normal adults there is a direct significant correlation between plasma cortisol and Type I and between plasma cortisol and Type II receptors in mononuclear leukocytes, while in Cushing's syndrome the correlation is inverse between plasma cortisol at 8 a.m. and Type II receptors. In an aged population the mean numbers of Type I and of Type II receptors are lower and plasma cortisol is higher than in adult controls, but the increase of plasma cortisol is not followed by a clinical picture of hypercorticism. Corticosteroid Type I and Type II receptors are inversely correlated with age. After dexamethasone suppression (1 mg at 11 p.m.) Type I receptors always decrease in controls while the response of Type II is not homogeneous. In an aged group of patients, both receptors are reduced by dexamethasone. We conclude that the decrease with age of corticosteroid receptors is possibly related to a physiological involution of corticosteroid receptors and that this reduction does increase plasma cortisol concentration, without affecting the glucocorticoid effector mechanism
Choice of diuretic therapy and reconsideration for aldosterone receptors blockers.
No full textIn an interesting editorial, Kaplan1 has focused recently on the choice of thiazide diuretics and concluded that chlorthalidone, alone or in addition to other antihypertensive drugs, may replace hydrochlorothiazide (HCTZ). The author also states that HCTZ and chlorthalidone, even at low doses (12.5 to 25.0 mg), can lower serum potassium and that an addition of small doses of spironolactone or eplerenone could provide maximal antihypertensive efficacy and prevent hypokalemia, particularly in resistant patients.
A very important issue dealing with all diuretics is the volume depletion and activation of the renin-angiotensin-aldosterone system. Diuretics, with the exception of aldosterone receptor blockers, do not directly affect mineralocorticoid receptors. Recent studies of the literature have shown that aldosterone, even in situations of normal sodium intake, can enhance oxidative stress through activation of NADPH oxidase in particular clinical situations. Aldosterone is involved in inflammation atherosclerosis and heart hypertrophy and fibrosis, and the addition of aldosterone receptor blockers prevents the risk of complications in patients with heart diseases treated with other drugs (Randomized Aldactone Evaluation Study and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study).
Concerning the secondary hyperaldosteronism from diuretics, Brown and colleagues2,3 have compared the effect of HCTZ (25 mg per day) with the effect of spironolactone on the fibrinolytic balance in hypertensive subjects. Although HCTZ and spironolactone increased angiotensin II and aldosterone, only HCTZ increased plasminogen activator inhibitor 1 antigen concentration. Mineralocorticoid receptor antagonism prevents the effect of activation of the renin-angiotensin-aldosterone system on the plasminogen activator inhibitor 1 antigen in normotensive subjects and improves the fibrinolytic balance in hypertensive subjects through a potassium-independent mechanism, the same pro-oxidative effect that is evident when administering triamterene, thus supporting the concept that aldosterone increases plasminogen activator inhibitor 1 synthesis independently from the potassium concentration.2,3
We have reported studies using human mononuclear leukocytes and have found that canrenone completely blocks the pro-oxidative effect of aldosterone in these cells, as measured by the protein expression of plasminogen activator inhibitor 1 and p22phox.4 In patients treated with thiazides or furosemide, aldosterone receptors are not blocked, and the cardiovascular risk is reduced by the lowering of blood pressure but is also enhanced by the binding of high aldosterone levels to mineralocorticoid receptors at the level of target tissues and, in particular, at the level of mononuclear leukocytes, a major component of vascular inflammation. This mechanism could enhance the fibrotic and atherogenic processes. These observations further enforce the concept that the goal of therapy is not only the lowering of blood pressure and the controlling of potassium but also the prevention of the inflammatory effect of aldosterone, as specified by Kaplan1 at the end of the editorial.
Aldosterone receptor blockers do have a limited use in essential and secondary hypertension, particularly in Europe, as demonstrated by the Guidelines of the European Council of Hypertension (New Consensus Hypertension Guidelines from European Society of Hypertension/European Society of Cardiology 2007: Antihypertensive Treatment), which considers thiazides but not aldosterone receptors blockers for treatment of resistant hypertension, and maybe aldosterone receptor blockers should have a larger prescription, considering that metabolites with minimal (potassium canrenoate and canrenone) or absent (eplerenone) antiandrogenic activity are available in many countries
Some considerations about evolutiuon of idiopathic primary aldosteronism
No full textThe prevalence of primary aldosteronism has increased since many patients who were previously considered as being affected by low renin essential hypertension are actually satisfying the new diagnostic criteria using plasma aldosterone/plasma renin activity (PRA) ratio. Many of these cases could be classified as subclinical hyperaldosteronism, having normal aldosterone and low PRA, or in alternative the normal range of aldosterone should be revised. Idiopathic hyperaldosteronism can, in many cases, be considered as an evolutive disease: it can be hypothesized that the biochemical picture can be preceded by essential hypertension and that, after several years, primary aldosteronism can evolve back to essential hypertension due to age-related reduced vascular and adrenal sensitivity to angiotensin II. This effect is also evident after long-term treatment with aldosterone receptors blockers and therefore it possible that aldosterone-receptors blockers are able to normalize the sensitivity of glomerulosa to angiotensin II even after long-term withdrawal. The use of aldosterone receptors blockers prevents cardiovascular complications due to local aldosterone effect at the level of endothelium and mononuclear leukocytes; therefore, these drugs should be also considered for therapy of patients with hypertension. It is not excluded that aldosterone receptor blockers could prevent the onset of idiopathic hyperaldosteronismand its complications in patients with hypertension without primary hyperaldosteronism. From all these considerations it follows that the concept of normal range of aldosterone should be revised and the use of aldosterone receptor blockers should be revisited
Aldosterone and thrombosis formation: Implications for ischemic and atherosclerotic heart disease
No full textAlterazioni della regolazione del cortisolo nel morbo di Alzheimer:possibili applicazioni nella diagnostica precoce
No full textWe trave studied 15 subjects affected by Alzheimer's disease and 15 healthy controls of the same age and sex. In all cases plasma cortisol (by enzymeimmunoassay) and Type I and TYPQ II corticosteroid receptors in mononuclear leukocytes (by radioreceptorassay) were measured. Results: plasma cortisol was significantly higher in Alzheimer's disease than in controls, while Type II corticosteroid receptor were significantly lower. From these results it is possible to postulate that in Alzbeimer's disease the agerelated alterations of the hypothalamic-pituitaric-adrenal axis are more evident or begin carlier. An hypothesis can also be formulated that the measurement of these parameters could be considered a precox sign of cerebral deterioration or of an acceleration of the aging process
Aldosterone, inflammation, and preeclampsia.
No full textWe would like to suggest that aldosterone could play an important role in the genesis of this increased susceptibility of inflammatory process in preeclampsia. This contention comes from a number of our studies that provide rationale for this possibility. We have demonstrated that in preeclampsia, plasma aldosterone and plasma progesterone are as high as in uncomplicated pregnancy, whereas the rectal subtractive potential difference, which is an index of biological effect of aldosterone, is increased only in preeclampsia to a similar extent as in primary aldosteronism.2 These data are consistent also with the measurement of aldosterone receptors in mononuclear leukocytes, whose number was normal in uncomplicated pregnancy and downregulated in preeclampsia, which, again, matched the changes observed in primary aldosteronism.3 We therefore suggested that uncomplicated pregnancy is characterized by a reduced response to the action of aldosterone. In addition, we have recently demonstrated that the coincubation of human mononuclear leukocytes from healthy subjects with high concentrations of aldosterone induces the expression of 2 inflammation and oxidative stress-related proteins, plasminogen activator inhibitor-1 and p22phox, as shown by Western blot analysis. In the same study, we have also shown that these effects of aldosterone were blocked by the aldosterone receptor antagonist canrenone.
Spontaneous resolution of idiopathic aldosteronism after long-term treatment with potassium canrenoate.
No full textThe results of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study4 and the Randomized Aldactone Evaluation Study5 in fact show that aldosterone receptor blockers are effective in preventing cardiovascular complications, independent from the aldosterone value. Our data can strengthen this concept, showing that aldosterone receptor blockers also have a beneficial effect at the level of glomerulosa, restoring a normal reactivity to angiotensin II.
In conclusion, our data are consistent either with an exhaustion of the biochemical picture of PA in patients treated for the long term with KC, with reversal of PA to essential hypertension, or with an age-related reduction of renin and aldosterone with restoration of normal reactivity of glomerulosa to aldosterone
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