Anti-aldosteronergic effect of torasemide

Uchida, Takeshi; Yamanaga, Katsumi; Nishikawa, Masakuni; Ohtaki, Yutaka; Kido, Hiroyuki; Watanabe, Masahiro

doi:10.1016/0014-2999(91)90812-5

Cited by 101 publications

(82 citation statements)

References 16 publications

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“…In particular, torasemide is known to have anti-aldosteronergic effects [34], and azosemide is known to have anti-arginine vasopressin effects [26]. Thus, direct comparisons of the effects of different loop diuretics should be made with caution.…”

mentioning

confidence: 99%

Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

Hori

Ohshima

Kanai

et al. 2010

The Journal of Veterinary Medical Science

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ABSTRACT. Our aim was to investigate the differences in the duration of diuretic effects and impact on the renin-angiotensin-aldosterone (RAA) system of furosemide as a model of short-and long-acting loop diuretics. Anesthetized dogs (n=6) were randomized into placebo, intravenous bolus administration (IB) and chronic rate infusion (CRI) groups. This study was conducted with a crossover study. Furosemide (4 mg/kg) was diluted to 18 mL in sterile saline. Furosemide was infused at 0.5 mg/kg/hr for 8 hr in the CRI group or was injected at 0 and 4 hr (both 2 mg/kg) in the IB group. Blood and urine samples were collected at baseline and at 1, 2, 4, 5, 6 and 8 hr. Compared with the baseline, the IB group had a significantly increased urine output at 1 and 5 hr. The CRI group had a significantly increased urine output persisting for 4 hr compared with the baseline. Compared with the placebo group, 8-hr urine output and 8-hr sodium excretion were significantly increased in the IB and CRI groups; the values in the CRI group were significantly higher than those in the IB group. Eight-hour potassium excretion was significantly increased in the IB and CRI groups. The plasma aldosterone concentration was significantly elevated in the IB group at 8 hr. Duration of action may be a predominant cause of loop diuretic-related differences. Persistent diuresis may cause greater diuretic effects than transient diuresis, with less elevation of the plasma aldosterone concentration.KEY WORDS: canine, diuretic resistance, loop diuretics, plasma aldosterone concentrations.J. Vet. Med. Sci. 72(1): 13-18, 2010 Loop diuretics are recommended as a first-line therapy in the management of congestive heart failure (CHF) and are important in the symptomatic treatment [19]. They can be divided into short-acting ones, such as furosemide, and long-acting ones, such as azosemide and torasemide. Although furosemide is commonly used in clinical settings, its main complication is that patients with CHF develop resistance to loop diuretics due to a reduction in the glomerular filtration rate and an increase in sodium reabsorption at diuretic-insensitive sites in the nephron [6,10,11,28]. Additionally, furosemide activates the renin-angiotensinaldosterone (RAA) system and the sympathetic nervous system [14,16,32].In contrast to furosemide, previous studies have revealed that long-acting loop diuretics have clinical efficacy; they cause less activation of the RAA system, reduce diuretic resistance, improve ventricular fibrosis and decrease the mortality rate in both humans and animal models [7,17,23,37]. Furosemide treatment for 14 days leads to diuretic resistance in dogs, but this does not occur with torasemide [17]. In human clinical study, the myocardial collagen volume decreases with torasemide, but remains unchanged with furosemide [23]. Additionally, a recent study showed that torasemide is associated with lower mortality compared with furosemide in patients with CHF [7]. Similarly, our previous data suggested that azosemide causes mild and long...

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confidence: 99%

Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

Hori

Ohshima

Kanai

et al. 2010

The Journal of Veterinary Medical Science

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“…This finding was attributed to an anti-aldosteronic effect of torasemide, which was absent in furosemide [47,48]. As shown recently, the regulation of collecting-duct Na + /K + -ATPase and K + excretion differs among loop diuretics.…”

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confidence: 62%

“…The question of whether TO also produces bradykinin and thus shows this additional mechanism to reduce K + excretion has not been investigated so far. There are, however, data such as a positive volume and NaCl excretion 24 h after dosing and a weaker kaliuretic effect of TO [32,46,47] that agree with piretanide data [50] but differ from those of furosemide [46,47,51].…”

Section: +mentioning

confidence: 95%

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Torasemide significantly reduces thiazide-induced potassium and magnesium loss despite supra-additive natriuresis

Knauf

Mutschler

Velázquez

et al. 2009

Eur J Clin Pharmacol

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Background Resistance to high-dose loop diuretics can be overcome either by co-administration with thiazides or by treatment with medium-dose loop diuretics combined with thiazides. Combination therapy has been proven to be superior to high-dose loop diuretic monotherapy for cardiac and renal edema. However, such a strongly efficacious short-term regimen is often complicated by undesired effects, including circulatory collapse and electrolyte disturbances. The question of whether the loop diuretic/ thiazide combinations are efficacious and safe when conventional doses are combined has not yet been answered. Methods The effects of hydrochlorothiazide (HCT) and torasemide (TO) given alone on the excretion of Na + , Cl -, K + , Mg 2+ , and Ca 2+ were compared with the effects of combined administration of the diuretics in 12 healthy volunteers. Results The co-administration of HCT (25 mg) with TO (5 or 10 mg) strongly increased Na + excretion. However, the combination significantly reduced K + and Mg 2+ excretion. The K + -sparing effect of the HCT/TO combination was shown to be due to a significant reduction in the HCTinduced increase in fractional K + excretion by the loop diuretic. Total excretion of Ca 2+ relative to Na + excretion was less with the HCT/TO combination than with TO given alone. Conclusion The enhancement of desired NaCl excretion by the HCT/TO combination with significant reduction of undesired loss of K + and Mg 2+ meets clinical requirements but has to be validated in long-term clinical trials.

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“…An important mediator of left ventricular and atrial fibrosis is the activation of mineralocorticoid receptors (MR) by aldosterone [10][11][12][13][14][15]. Interestingly, experimental and human studies have reported that torasemide, but not furosemide, may exert anti-aldosterone effects [16] [17,18]. However, the underlying mechanisms and the consequences of these observations are only partially understood, especially in the context of atrial fibrillation.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice

Adam

Zimmer

Hanke

et al. 2015

Journal of Molecular and Cellular Cardiology

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Anti-aldosteronergic effect of torasemide

Cited by 101 publications

References 16 publications

Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

Torasemide significantly reduces thiazide-induced potassium and magnesium loss despite supra-additive natriuresis

Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice

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