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At least 721 records · Page 40Linked to original sources
PubMed1997

Mineralocorticoid (type I) receptors in the olfactory mucosa of the mammal: studies with [3H]aldosterone and the anti-mineralocorticoid spironolactone.

High-affinity, specific binding sites to mineralocorticoids, with characteristics of mineralocorticoid (type I) receptors, have been found in the mammalian olfactory mucosa. In the presence of RU 28362, which blocks low-affinity binding of the labeled hormone to glucocorticoid (type II) receptors, Scatchard analysis of the specific [3H]aldosterone binding indicates that aldosterone binds to a single class of high-affinity (type I) sites with a dissociation constant, Kd, of 1.2 x 10(-9) M and a maximum number of binding sites, Bmax, of 63 fmol/mg dry tissue. Time course of association of [3H]aldosterone and its binding sites showed maximal binding by 30 min at 25 degrees C which remained unchanged up to 90 min. Competition studies performed with 1 x 10(-7)-1 x 10(-5) M spironolactone, a competitive mineralocorticoid antagonist, showed a dose-response reduction of [3H]aldosterone binding, implying that in the olfactory mucosa this compound behaves as an aldosterone antagonist. These results demonstrate significant [3H]aldosterone binding to receptors of high affinity and mineralocorticoid specificity and suggest that the olfactory mucosa is a target site for mineralocorticoid action.

Aldosterone↗
PubMed2003

Hyperkalaemia in congestive heart failure patients using ACE inhibitors and spironolactone.

BACKGROUND: Recent studies have shown a fall in global mortality with minimal side effects in severe congestive heart failure (CHF) patients receiving angiotensin-converting enzyme inhibitors (ACEI) plus spironolactone (SLN). However, the risk of hyperkalaemia due to ACEI may be increased by the concomitant use of SLN. METHODS: We conducted a retrospective cohort study by examining consecutive cases of severe decompensated CHF admitted to a university hospital in Brazil from March 1999 to March 2000, which had used ACEI with or without SLN. We reviewed charts for the 30 days following admission and assessed various therapeutic regimens used for heart failure as well as serum potassium and creatinine, before and after drug exposure. The primary end-point was the development of hyperkalaemia (K > or = 5.5 mEq/l). For analysis, the subjects were split into patients treated with ACEI/SLN (n = 49) and patients treated with ACEI (n = 51) by itself. RESULTS: Although demographical and clinical features were comparable between the two groups, ACEI/SLN patients had a higher proportion of class IV CHF. We found 16 cases of hyperkalaemia in ACE/SLN patients, but only one case in ACEI subjects. The odds ratio for developing hyperkalaemia in ACEI/SLN patients was 24. When class III CHF subjects were excluded, the odds ratio was 14.6 (95% confidence interval: 1.8-119.6). The best predictors of hyperkalaemia were class IV CHF, increases in creatinine following treatment and diabetes. CONCLUSIONS: Patients with severe decompensated CHF using ACEI with SLN are at major risk for developing hyperkalaemia.

Adult↗
PubMed1985

Modifications of the gonadal function in the adult rat after fetal exposure to spironolactone.

The effects of fetal exposure to spironolactone (SPL), an aldosterone antagonist with weak antiandrogen and gestagen properties, upon the pituitary-gonadal axis were studied in the offspring of rats that had been treated daily from gestation day 14 to day 20 with 10 or 20 mg SPL or the solvent vehicle (for controls). At 70-80 days of age, SPL-exposed rats showed no alterations in external genitalia or in body weight. However, males displayed a dose-dependent decrease in the weights of the ventral prostate and seminal vesicles. Whereas basal and gonadotropin-releasing hormone (GnRH)-induced plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and 5 alpha-dihydrotestosterone levels were similar to controls, basal plasma and pituitary prolactin (Prl) levels were reduced (SPL-exposed 6.8 +/- 1.0 vs. controls 15.8 +/- 2.8 ng/ml and 6.1 +/- 1.2 vs. 11.6 +/- 1.8 microgram/anterior pituitary gland; mean +/- SEM). Cytosolic androgen receptors in ventral prostate were nonsignificantly decreased, but they increased after GnRH in contrast to controls. Nuclear androgen receptors were normal. Females displayed normal estrous cycles. Basal and GnRH-induced plasma FSH, Prl, estradiol, and progesterone concentrations were similar to controls, whereas plasma LH was elevated. Estrogen receptors in uterine cytosol were low and increased after GnRH. Ovaries and uteri were enlarged. The present study demonstrates that in utero exposure to SPL leads to endocrine dysfunctions that persist into adulthood. They are characterized in males by hypoprolactinemia, reduced weights of accessory sex organs, and a suggestion of functional modifications of androgen receptors. In females they are characterized by increased LH secretion, increased ovarian and uterine weights, and decreased uterine cytosol estrogen receptors, suggesting enhanced estrogenic action.

Animals↗
PubMed2003

Combined effects of low-dose oral spironolactone and captopril therapy in a rat model of spontaneous hypertension and heart failure.

The effects of low-dose oral spironolactone (SPIRO) in a rat model of hypertensive heart failure (spontaneously hypertensive heart failure rat) were compared with its effects when combined with captopril (CAP). Twenty-six spontaneously rats with hypertensive heart failure were treated with either placebo (CON), SPIRO (20 mg/kg/d by mouth), CAP (100 mg/kg/d by mouth), or both SPIRO and CAP for 12 weeks. This dose of oral SPIRO did not affect blood pressure, left ventricular end-diastolic diameter, left ventricular ejection fraction, plasma atrial natriuretic peptide concentration, or cardiac fibrosis; however, in combination with CAP, it exerted a significant depressor effect after 12 weeks of treatment that was accompanied by increased urine output and decreased urinary protein excretion. These effects were significantly greater than those with CAP treatment alone. A significant increase in plasma aldosterone level was observed only in CON (174 +/- 21%). These data suggest that the addition of low-dose SPIRO to angiotensin I-converting enzyme inhibitor treatment may prevent progression into end-stage congestive heart failure through synergistic effects on diuresis and renoprotection.

Administration, Oral↗
PubMed1995

Effects of topically applied spironolactone on androgen stimulated sebaceous glands in the hamster pinna.

The effects of spironolactone (5% SYC-201G, a preparation developed for clinical use in acne vulgaris by Searle Yakuhin K.K.), which is known to have antiandrogenic effects by competitively inhibiting dihydrotestosterone at androgen receptor sites, was topically applied to the androgen stimulated sebaceous glands of adult female golden hamsters. Androgen stimulation, induced by intramuscular injection of testosterone propionate (TP) every other day over a two week period, resulted in a 2.5 to 2.7 time increase in the size of the sebaceous glands of the hamster pinna. Once-daily treatment with 5% SYC-201G or matching placebo was applied to androgen-stimulated hamsters on one pinna only during the same period as TP injection. Comparison between the treated and untreated sides revealed a significant suppression in the sebaceous gland size (p < 0.05) by 5% SYC-201G; no such effect was observed with placebo. The difference in the suppression rate of the sebaceous gland size between 5% SYC-201G (23%) and matching placebo (-4.7%) was significant (p < 0.01).

Administration, Topical↗
PubMed2003

Becker's nevus with ipsilateral breast hypoplasia: improvement with spironolactone.

Ipsilateral breast hypoplasia is a rare abnormality in Becker's nevus. The pathogenesis of the breast hypoplasia is not understood, but an increased level of androgenic receptor in the affected area may play a role. We report a case of Becker's nevus with ipsilateral breast hypoplasia. Spironolactone, an anti-androgenic agent, was tried for treatment of the hypoplasia, and, one month later, breast enlargement was seen in only the hypoplastic breast with Becker's nevus. This finding supports the theory that breast hypoplasia in Becker's nevus is related to an increase in androgenic receptor.

Adolescent↗
PubMed2007

Treatment of female pattern hair loss with a combination of spironolactone and minoxidil.

A 53-year-old woman with clinical evidence of female pattern hair loss and histological evidence of androgenetic alopecia was initially treated with the oral antiandrogen spironolactone 200 mg daily. Serial scalp photography documented hair regrowth at 12 months; however, the hair regrowth plateaued, and at 24 months there had been no further improvement in hair density. Twice daily therapy with topical minoxidil 5% solution was then introduced and further regrowth documented, confirming the additive effect of combination therapy.

Administration, Cutaneous↗
PubMed1990

A case of testosterone-secreting adrenal cortical adenoma with spironolactone body-like inclusion.

Testosterone-secreting adrenal adenoma is rare. We recently experienced a 17-year-old pubertal girl who showed signs of virilization and a high serum level of testosterone. The excised adrenal gland showed a 3.5 x 3 x 3-cm cortical adenoma. Light and electron microscopic findings together with the high serum level and high tumor tissue contents of testosterone and dehydroepiandrosterone (DHA) indicated that the tumor was a testosterone-secreting adrenal cortical adenoma. This appears to be a rather rare tumor from a review of the literature. Interestingly, in this case, the cytoplasm of the tumor cells contained structures resembling spironolactone bodies. From the results of enzyme histochemistry, the steroidogenetic pathways in this tumor were speculated.

Acid Phosphatase↗
PubMed2006

Spironolactone with ACE inhibitor is effective in gross hematuria caused by nephroptosis.

Gross hematuria caused by nephroptosis is difficult to treat and sometimes requires surgical treatment. We experienced a case of a 64-year-old woman with gross hematuria due to nephroptosis and glomerular thin basement membrane that showed remission of hematuria with the blockade of the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor and spironolactone.

Biopsy↗
PubMed1975

Effect of high dose spironolactone and chlorthalidone in essential hypertension: relation to plasma renin activity and plasma volume.

The effect on blood pressure of high (400 mg/day-S400) and moderate dose (200 mg/day-S200) spironolactone and chlorthalidone (100 mg/day-C100), given in a random double-blind manner was related to plasma renin activity and plasma volume in 38 essential hypertensives. The fall in pressure from a control of 154/103 mm Hg was essentially the same after four weeks of each drug--S400 deltaBP 24/13 mm, S200 18/9 mm, C100 17/12 mm (all P less than 0-001). Twelve of 37 patients (32%) had low initial renin, but this appeared as responsive to the chlorthalidone stimulus as that of the normal renin group. The antihypertensive effect of all regimens was unrelated to plasma renin activity. Plasma volume was significantly lowered at the end of each treatment period, but the decline could not be correlated with blood pressure effects. Patients with initially low plasma volume were more likely to respond to S400 (r = 0-545, P less than 0-001), whereas the antihypertensive effect of the S200 and C100 regimens was independent of this variable.

Adult↗
PubMed1986

Combined spironolactone and converting-enzyme inhibitor therapy for refractory heart failure.

Three cases are described of severe congestive heart failure which failed to respond to digitalis, high doses of loop diuretics, and converting-enzyme inhibitors. The addition of spironolactone produced a substantial diuresis associated with clinical and radiological improvement in each case. Although a reversible deterioration in renal function was observed, this drug combination represents a therapeutic option in end-stage heart failure.

Adult↗
PubMed1979

Treatment of premenstrual syndrome by spironolactone.

Spironlactone was given to 28 women in a double blind cross over trial during four menstrual cycles. Hormonal profiles were measured during the first two cycles. Plasma aldosterone was elevated in the premenstrual phase of the cycles but there was no significant difference between symptomatic and asymptomatic groups. The rise in serum progesterone was higher in the symptomatic group during the postovulatory phase. The administration of spironolactone reduced weight and relieved psychological symptoms in more than 80 per cent of the symptomatic group.

Aldosterone↗
PubMed1985

Spironolactone in combination with an oral contraceptive: an alternative treatment for hirsutism.

The clinical efficacy of a combination of spironolactone and an oral contraceptive pill (Conova 30) was assessed in 23 patients presenting with hirsutism of whom 20 completed 6 months of treatment. Of the 20 patients, 16 showed improvement on objective (Ferriman & Gallwey hair score) and subjective assessment. Serum levels of androgens (testosterone, androstenedione and 17-hydroxy progesterone) were suppressed and sex hormone binding globulins were elevated. Nausea was the only significant side effect.

Contraceptives, Oral, Combined↗
PubMed1976

Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and oestradiol.

Using infrared spectroscopy, X-ray diffractometry, differential thermal analysis, scanning electron microscopy, solubility and dissolution rate measurements, it was demonstrated that the comminution of digoxin results in the appearance of an amorphous phase. The examination of spironolactone and 17 beta-oestradiol by infrared spectroscopy and differential thermal analysis showed that these compounds also undergo changes in their crystallinity on grinding. Since the dissolution characteristics of poorly soluble drugs may be complex functions of surface area and crystallinity, it is concluded that the most pertinent method for standardizing a sample of a polymorphic drug of low solubility is by means of a powder dissolution test, as the results embrace the influences of particle size, aggregation and polymorphism.

Chemistry, Pharmaceutical↗
PubMed2006

Induction of rat intestinal P-glycoprotein by spironolactone and its effect on absorption of orally administered digoxin.

The effect of the diuretic spironolactone (SL) on expression and function of intestinal P-glycoprotein (P-gp), as well as its impact on intestinal absorption of digoxin, was explored. Rats were treated with daily doses of 200 micromol/kg b.wt. of SL intraperitoneally for 3 consecutive days. The small intestine was divided into four equal segments of approximately 25 cm, with segment I being the most proximal. Brush-border membranes were isolated and used in analysis of P-gp expression by Western blot analysis. P-gp content increased in the SL group by 526, 292, 210, and 622% over controls for segments I, II, III, and IV, respectively. Up-regulation of apical P-gp was confirmed by immunofluorescence microscopy. P-gp transport activity was explored in intestinal sacs prepared from segment IV using two different model substrates. Serosal to mucosal transport (efflux) of rhodamine 123 was 140% higher, and mucosal to serosal transport (absorption) of digoxin was 40% lower in the SL group, both indicating increased P-gp function. In vivo experiments showed that intestinal absorption of a single dose of digoxin administered p.o. was attenuated by SL pretreatment. Thus, concentration of digoxin in portal and peripheral blood was lower in SL versus control groups, as well as its accumulation in kidney and liver. Urinary excretion of digoxin was significantly decreased in the SL group, probably reflecting decreased systemic availability of digoxin for subsequent urinary elimination. We conclude that SL induces P-gp expression with potential impact on intestinal absorption of substrates with therapeutic application.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Environmental xenobiotics and the antihormones cyproterone acetate and spironolactone use the nuclear hormone pregnenolone X receptor to activate the CYP3A23 hormone response element.

The pregnenolone X receptor (PXR), a new member of the nuclear hormone receptor superfamily, was recently demonstrated to mediate glucocorticoid agonist and antagonist activation of a hormone response element spaced by three nucleotides (DR-3) within the rat CYP3A23 promoter. Because many other steroids and xenobiotics can up-regulate CYP3A23 expression, we determined whether some of these other regulators used PXR to activate the CYP3A23 DR-3. Transient co-transfection of LLC-PK1 cells with (CYP3A23)2-tk-CAT and mouse PXR demonstrated that the organochlorine pesticides transnonachlor and chlordane and the nonplanar polychlorinated biphenyls (PCBs) each induced the CYP3A23 DR-3 element, and this activation required PXR. Additionally, this study found that PXR is activated to induce (CYP3A23)2-tk-CAT by antihormones of several steroid classes including the antimineralocorticoid spironolactone and the antiandrogen cyproterone acetate. These studies reveal that PXR is involved in the induction of CYP3A23 by pharmacologically and structurally distinct steroids and xenobiotics. Moreover, PXR-mediated PCB activation of the (CYP3A23)2-tk-CAT may serve as a rapid assay for effects of nonplanar PCBs.

Androgen Antagonists↗
PubMed1970

Mercury poisoning: prevention by spironolactone.

The renal tubular necrosis and calcification as well as the mortality induced by mercuric chloride in the rat are readily prevented by prior treatment with well-tolerated amounts of spironolactone.

Acute Kidney Injury↗