Antiarrhythmic activity of potassium canrenoate in man

Yeh, Billy K.; Chiang, Benjamin N.; Sung, Pei-Kun

doi:10.1016/s0002-8703(76)80112-3

Cited by 22 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A spironolactone analogue for intravenous use (potassium canrenoate) has been claimed to possess antiarrhythmic properties, especially in arrhythmias induced by digitalis. 11 …”

Section: Discussionmentioning

confidence: 99%

Spironolactone‐induced changes in digoxin kinetics

Waldorff

Andersen

Heebøll-Nielsen

et al. 1978

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Plasma clearance, volumes of distribution, and renal and extrarenal clearances of digoxin were calculated from plasma digoxin concentrations and urinary excretion of digoxin after intravenous injection of digoxin in 8 subjects. The investigation was repeated in the same subjects during long-term treatment with spironolactone. Increased plasma concentration of digoxin was detected during spironolactone treatment. Calculated plasma and renal clearances of digoxin and the volumes of distribution decreased statistically significant. Near maximal capacity for the tubular secretion of digoxin was found when normal digoxin dosage was used. It is suggested that unless spironolactone decreases the myocardial sensitivity for digoxin, the loading dose as well as the maintenance dose of digoxin should be reduced during treatment with spironolactone.

show abstract

“…A spironolactone analogue for intravenous use (potassium canrenoate) has been claimed to possess antiarrhythmic properties, especially in arrhythmias induced by digitalis. 11 …”

Section: Discussionmentioning

confidence: 99%

Spironolactone‐induced changes in digoxin kinetics

Waldorff

Andersen

Heebøll-Nielsen

et al. 1978

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

show abstract

“…Subsequently spironolactone and its active metabolite, canrenone (Figure 1b), were reported to reverse digitalis toxicity [14], and to lower blood pressure in rat hypertension models, in which levels of CTS are elevated [5,15,16]. Most recently spironolactone was reported to suppress cardiac fibrosis in rats chronically treated by MBG [7].…”

Section: Introductionmentioning

confidence: 99%

Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists

Федорова

Емельянов

Bagrov

et al. 2015

Journal of Hypertension

View full text Add to dashboard Cite

Objective Endogenous cardiotonic steroids (CTS), including marinobufagenin (MBG), stimulate vascular synthesis of collagen. Because mineralocorticoid antagonists competitively antagonize effect of CTS on the Na/K-ATPase, we hypothesized that spironolactone would reverse the pro-fibrotic effects of MBG. Methods Experiment 1. Explants of thoracic aortae and aortic vascular smooth muscle cells (VSMC) from Wistar rats were cultured for 24 hours in the presence of vehicle or MBG (100 nmol/L) with or without canrenone (10 µmol/L), an active metabolite of spironolactone. Experiment 2. In 16 patients (56 ± 2 yrs) with resistant hypertension (RH) on a combined (Lisinopril / amlodipine / hydrochlorothiazide) therapy, we determined arterial pressure, pulse wave velocity (PWV), plasma MBG, and erythrocyte Na/K-ATPase before and six months after addition of placebo (n=8) or spironolactone (50 mg/day; n=8) to the therapy. Results In rat aortic explants and in VSMC, pretreatment with MBG resulted in a two-fold rise in collagen-1, and a marked reduction in the sensitivity of the aortic rings to the vasorelaxant effect of sodium nitroprusside following endothelin-1-induced constriction (EC50=480±67 nmol/L vs. 23±3 nmol/L in vehicle-treated rings; P<0.01). Canrenone blocked effects of MBG on collagen synthesis and restored sensitivity of vascular rings to sodium nitroprusside (EC50 = 17±1 nmol/L). RH patients exhibited elevated plasma MBG (0.42 ± 0.07 vs. 0.24 ± 0.03 nmol/L; P=0.01) and reduced Na/K-ATPase activity (1.9 ± 0.15 vs 2.8 ± 0.2 µmol Pi/ml/hr, P<0.01) vs. 7 healthy subjects. Six-month administration of spironolactone, unlike placebo treatment, was associated with a decrease in PWV and arterial pressure, and with restoration of Na/K-ATPase activity in the presence of unchanged MBG levels. Conclusion MBG-induced vascular fibrosis is a likely target for spironolactone.

show abstract

“…Although Aldo antagonists are used in the treatment of hypertension [6,7] and myocar dial infarction [18][19][20], little is known about the direct cardiac effects of these pharmaco logical agents. A few studies on their effects on cardiac tissue (e.g., papillary muscles, isolated atria, and ventricular strips) have been pub lished, but the response of the intact heart to such agents has received little attention.…”

Section: Discussionmentioning

confidence: 99%

“…The antagonists of Aldo have also been described as antiarrhythmic agents in studies of animal models [14][15][16][17], Indeed, potassium salts are used as antiarrhythmic drugs in clini cal practice [18][19][20], However, the mecha nisms of action of these agents remain un known, and no study on the cardiac effects of Aldo and its antagonists has been reported to date.…”

Section: Introductionmentioning

confidence: 99%

Effects of Aldosterone and Spironolactone on the Isolated Perfused Rat Heart

Moreau¹,

Chardigny²,

Rochette³

1996

Pharmacology

View full text Add to dashboard Cite

Aldosterone antagonists are used in the treatment of hypertension. However, the cardiac influences of aldosterone and its antagonists have not been thoroughly investigated. In the present study, we investigated the effects of aldosterone and spironolactone on an isolated rat working heart model. Aldosterone (10^–8 mol/l) decreased the coronary flow and increased aortic flow and cardiac output. Spironolactone (10^–5 mol/l) inhibited these effects. These results suggest that aldosterone directly influences the cardiac function. Spironolactone appears able to inhibit the adverse cardiac effects of aldosterone. The exact mechanisms remain to be elucidated, but the early effects of aldosterone under our experimental conditions on the functional parameters of the heart suggest a nongenomic response including activation of receptors different from those transmitting genomic steroid actions.

show abstract

Antiarrhythmic activity of potassium canrenoate in man

Cited by 22 publications

References 14 publications

Spironolactone‐induced changes in digoxin kinetics

Spironolactone‐induced changes in digoxin kinetics

Marinobufagenin-induced vascular fibrosis is a likely target for mineralocorticoid antagonists

Effects of Aldosterone and Spironolactone on the Isolated Perfused Rat Heart

Contact Info

Product

Resources

About