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Aldosterone excess or escape: Treating resistant hypertension.
Ubaid-Girioli, S, Adriana de Souza, L, Yugar-Toledo, JC, Martins, LC, Ferreira-Melo, S, Coelho, OR, Sierra, C, Coca, A, Pimenta, E, Moreno, H
Journal of clinical hypertension (Greenwich, Conn.). 2009;(5):245-52
Abstract
Aldosterone excess or "escape" can occur after treatment with medications that block the renin-angiotensin-aldosterone system or in undiagnosed primary aldosteronism. Spironolactone is thought to be an important addition to resistant hypertension (RH) treatment. In this study, resistant (RH) and controlled (CH) hypertensives and normotensive patients were submitted to echocardiography, flow-mediated vasodilation, carotid intima-media wall thickness studies, renin plasma activity, and aldosterone plasma levels and plasma and urinary sodium and potassium concentrations at baseline (pre-spironolactone phase). Subsequently, for only RH and CH groups, 25 mg/d spironolactone was added to preexisting treatments over 6 months. Afterwards, these parameters were reassessed (post-spironolactone phase). The RH and CH groups achieved reductions in blood pressure (P<.001), decreases in left ventricular hypertrophy (P<.001), improved diastolic function (Kappa index RH: 0.219 and Kappa index CH: 0.392) and increases in aldosterone concentrations (P<.05). The RH group attained improved endothelium-dependent (P<.001) and independent (P=.007) function. Optimized RH treatment with spironolactone reduces blood pressure and improves endothelial and diastolic function and left ventricular hypertrophy despite the presence of aldosterone excess or escape.
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2.
The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome.
Garland, EM, Raj, SR, Black, BK, Harris, PA, Robertson, D
Neurology. 2007;(8):790-8
Abstract
BACKGROUND Previous studies of patients with postural tachycardia syndrome (POTS) have been hampered by relatively small cohorts, failure to control medications and diet, and inconsistent testing procedures. METHODS The Vanderbilt Autonomic Dysfunction Center Database provided results of posture studies performed in 165 patients and 66 normal controls after dietary and medication restrictions. All posture studies were performed after an overnight fast and > or =30 minutes of supine rest. RESULTS In both the supine and standing positions, heart rate (HR) and plasma concentrations of norepinephrine (NE), epinephrine, and dopamine were higher in patients with POTS compared with the healthy controls. Supine diastolic blood pressure (BP) was also elevated in POTS, whereas supine plasma l-3,4-dihydroxyphenyalanine was reduced. In an analysis of patient subgroups with either an upright plasma NE > or = 3.54 nM (high NE) or an upright plasma NE < 3.54 nM (normal NE), HR and BP were greater in the patient subgroup with high NE. In addition to these significant differences in hemodynamic and catechol measurements, we demonstrated that supine and standing plasma aldosterone and the aldosterone/renin ratio were decreased in patients with POTS. Plasma renin activity (PRA) tended to be higher in patients, and standing HR for those in the highest PRA quartile was significantly greater than for those in the lowest PRA quartile. CONCLUSIONS Our results from larger cohorts of patients and controls than previously studied confirm published findings and contribute additional evidence of sympathetic activation in postural tachycardia syndrome (POTS). Abnormalities in the renin-angiotensin-aldosterone system may also contribute to the POTS phenotype.
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3.
Aldosterone escape during blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy is associated with enhanced decline in glomerular filtration rate.
Schjoedt, KJ, Andersen, S, Rossing, P, Tarnow, L, Parving, HH
Diabetologia. 2004;(11):1936-9
Abstract
AIMS/HYPOTHESIS It has been suggested that aldosterone plays a role in the initiation and progression of renal disease independently of arterial blood pressure and plasma angiotensin II levels. We evaluated the influence of plasma aldosterone levels on progression of diabetic nephropathy during long-term blockade of the renin-angiotensin-aldosterone system. METHODS A total of 63 hypertensive patients with type 1 diabetes and diabetic nephropathy were treated with losartan, 100 mg once daily, for a mean follow-up period of 35 months. Plasma aldosterone, GFR, albuminuria and 24-h blood pressure were determined at baseline and at regular intervals during the study. RESULTS Patients were divided according to their increasing or decreasing levels of plasma aldosterone during long-term losartan treatment in an escape group (n=26) and a non-escape group (n=37). In the escape group, aldosterone levels increased from (geometric mean [95% CI]) 57 pg/ml (43-76 pg/ml) at 2 months, to 102 pg/ml (78-134 pg/ml) at the end of the study (p<0.01). The corresponding levels in the non-escape group were 83 pg/ml (69-102 pg/ml) and 49 pg/ml (40-60 pg/ml; p<0.01). The median rate of decline in GFR was 5.0 ml.min(-1).year(-1) (range 0.4-15.9 ml.min(-1).year(-1)) in the escape group, compared with 2.4 ml.min(-1).year(-1) (-1.6 to 11.0 ml.min(-1).year(-1)) in the non-escape group (p<0.005). The increase in plasma aldosterone correlated with the rate of decline in GFR (r(2)=0.19, p<0.001), corresponding to a decline in GFR of 1.5 ml.min(-1).year(-1) for every two-fold increase in plasma aldosterone. Pre-treatment and treatment values of plasma aldosterone were not related to albuminuria or to changes in albuminuria during the study. CONCLUSIONS/INTERPRETATION Our data suggest that aldosterone escape during long-term blockade of the renin-angiotensin-aldosterone system is associated with an enhanced decline in GFR in patients with type 1 diabetes and diabetic nephropathy.
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4.
Characterization of serotonin(4) receptors in adrenocortical aldosterone-producing adenomas: in vivo and in vitro studies.
Lefebvre, H, Cartier, D, Duparc, C, Lihrmann, I, Contesse, V, Delarue, C, Godin, M, Fischmeister, R, Vaudry, H, Kuhn, JM
The Journal of clinical endocrinology and metabolism. 2002;(3):1211-6
Abstract
We have previously shown that serotonin (5-HT) stimulates aldosterone secretion from the human adrenal gland through activation of 5-HT(4) receptors. The aim of the present study was to investigate in vivo and in vitro the presence of 5-HT(4) receptors in aldosterone-producing adenomas (aldosteronomas). Eight patients with aldosteronoma received a single oral dose of placebo or cisapride (10 mg). Cisapride administration significantly increased plasma aldosterone within 120 min without any significant change in renin, cortisol, or potassium levels. In two patients, a marked decrease in the plasma aldosterone response to cisapride was observed after surgical removal of the tumor. The effects of 5-HT and selective 5-HT(4) ligands on aldosterone production from aldosteronoma tissues were studied in vitro using a perifusion system technique. 5-HT and the 5-HT(4) receptor agonist cisapride (10(-7) M, 20 min) both stimulated aldosterone secretion from aldosteronoma slices. The 5-HT- and cisapride-evoked aldosterone responses were inhibited by concomitant administration of the specific 5-HT(4) receptor antagonist GR 113808 (10(-7) M, 150 min). PCR amplification revealed the expression of 5-HT(4) receptor mRNA in 13 of 14 aldosteronomas studied. Taken together, these data show that most aldosteronomas, like normal glomerulosa cells, express a functional 5-HT(4) receptor. Our results also suggest that 5-HT, which can be locally released by intratumoral mast cells, may play a role in the pathophysiology of these tumors.
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5.
Orthostatic tolerance and hormonal changes in women during 120 days of head-down bed rest.
Maillet, A, Zaouali-Ajina, M, Vorobiev, D, Blanc, S, Pastouchkova, L, Reushkina, G, Morukov, B, Grigoriev, AI, Gharib, C, Gauquelin-Koch, G
Aviation, space, and environmental medicine. 2000;(7):706-14
Abstract
BACKGROUND Women will be included as mission specialists in the upcoming International Space Station program. This paper describes the changes in volume-regulating hormones and determines the degree of degradation in orthostatic tolerance in a group of women after 120 d of bed rest. The aim of this study was to test a countermeasure program to be used by women during long-duration spaceflights. METHODS For 120 d of -6 degrees head-down bed rest (HDBR), eight healthy women were assigned either to a no-countermeasure (No-CM, n = 4), or to a countermeasure (CM, n = 4) group. In the countermeasure group, exercise began after 2 wk, pharmacological agents were given during the 1st and 3rd mo, and the "Centaur" suit was worn on the last day of bed rest and during the day time for several days after bed rest. Diet supplements were taken during the 1st and 4th mo of HDBR. Tilt tests were run before and after HDBR. RESULTS After the HDBR, none of the CM subjects, had pre-syncopal or syncopal symptoms during tilt tests: BP was well maintained in the CM group, while heart rate and BP changed in the No-CM group. In plasma, atrial natriuretic peptide (ANP) increased in both groups and remained high throughout HDBR, while aldosterone increased and remained elevated in the No-CM group. Natriuresis was decreased during HDBR. CONCLUSION The CM protocols used during this study were efficient and prevented orthostatic intolerance for the four CM subjects. It would be necessary to obtain more data regarding this set of CM protocols on female subjects to lead to statistical and formal conclusions.