Tolvaptan Attenuates Left Ventricular Fibrosis After Acute Myocardial Infarction in Rats

Yamazaki, Takanori; Nakamura, Yasuhiro; Shiota, Masayuki; Osada‐Oka, Mayuko; Fujiki, Hiroyuki; Hanatani, Akihisa; Shimada, Kenei; Miura, Katsuyuki; Yoshiyama, Minoru; Itoh, Hiroshi; Izumi, Yasukatsu

doi:10.1254/jphs.13086fp

Cited by 9 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the same time, tolvaptan was shown to attenuate MI-induced mRNA expression of atrial and brain natriuretic peptides, which are reliable markers of heart failure (28), as well as monocyte chemotactic protein-1, transforming growth factor-b1, and endothelin-1 in the marginal infarct region (29). Furthermore, a 2-week treatment with tolvaptan improved the left ventricular ejection fraction and suppressed MI-induced left ventricular interstitial fibrosis and mineralocorticoid receptor expression in rats with acute heart failure after MI (30). These observations suggest that tolvaptan may have beneficial effects both on acute and chronic heart failure, which is partially mediated by the suppression of neurohumoral activation, the renin-angiotensinaldosterone system, and inflammation.…”

Section: Experimental Animal Modelsmentioning

confidence: 99%

Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure

2014

Self Cite

View full text Add to dashboard Cite

Abstract. Arginine vasopressin (AVP) is a 9-amino acid peptide that is secreted from the posterior pituitary in response to high plasma osmolality and hypotension. AVP has important roles in circulatory and water homoeostasis, which are mediated by oxytocin receptors and by AVP receptor subtypes: V 1a (mainly vascular), V 1b (pituitary), and V 2 (renal). Vaptans are orally and intravenously active nonpeptide vasopressin-receptor antagonists. Recently, subtype-selective nonpeptide vasopressin-receptor agonists have been developed. A selective V 1a -receptor antagonist, relcovaptan, has shown initial positive results in the treatment of Raynaud's disease, dysmenorrhea, and tocolysis. A selective V 1b -receptor antagonist, nelivaptan, has beneficial effects in the treatment of psychiatric disorders. Selective V 2 -receptor antagonists including mozavaptan, lixivaptan, satavaptan, and tolvaptan induce highly hypotonic diuresis without substantially affecting the excretion of electrolytes. A nonselective V 1a /V 2 -receptor antagonist, conivaptan, is used in the treatment for euvolaemic or hypervolemic hyponatremia. Recent basic and clinical studies have shown that AVP-receptor antagonists, especially V 2 -receptor antagonists, may have therapeutic potential for heart failure. This review presents current information about AVP and its antagonists.

show abstract

Section: Experimental Animal Modelsmentioning

confidence: 99%

Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure

2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…(6,7) Thus, tolvaptan has been shown to inhibit fibrosis in myocardium, which does not have V2 receptors. In addition, tolvaptan has been demonstrated to exert anti-inflammatory action and inhibit expression of TGF-β1 and collagen I mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…(6,7) Fascinatingly, tolvaptan has also been reported to inhibit fibrosis in myocardium, which does not have V2 receptors. (8) …”

Section: Introductionmentioning

confidence: 99%

Effectiveness of tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy for hepatoprotection and diuresis in a rat cirrhotic model

Tanabe

Takami

Fujisawa

et al. 2017

J. Clin. Biochem. Nutr.

View full text Add to dashboard Cite

Spironolactone and furosemide, which are used to treat ascites associated with decompensated cirrhosis, are ineffective in treating refractory ascites. Hence, combination therapy with tolvaptan, a vasopressin V2 receptor antagonist, has been approved in Japan. Tolvaptan monotherapy and combination therapy with furosemide inhibit fibrosis in cardiac remodeling; hence, we examined these therapies in a rat cirrhotic model, including their usefulness in inhibiting hepatic fibrosis. In the present study, we used a model of hepatic fibrosis induced by a choline-deficient l-amino-acid-defined diet + diethylnitrosamine. Rats were divided into a low-dose furosemide group (15 mg/kg/day), a high-dose furosemide group (100 mg/kg/day), a tolvaptan monotherapy group (10 mg/kg/day), a low-dose furosemide/tolvaptan combination therapy group, and a control group which received neither furosemide nor tolvaptan; we then assessed diuretic effects and hepatic fibrosis. The tolvaptan monotherapy group and the furosemide/tolvaptan combination therapy group demonstrated significantly higher urine volume than the control group and the low-dose furosemide group. In addition, tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy were found to inhibit hepatic fibrosis and yield a hepatoprotective effect by an antioxidative mechanism. The results of the present study suggest that tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy are highly effective for hepatoprotection and diuresis.

show abstract

“…Tolvaptan increased urine output without increasing urine sodium excretion, plasma renin activity, or plasma aldosterone, but it had no effect on cardiac remodeling, cardiac function, or survival in a model of autoimmune myocarditis (40,41). Tolvaptan alone or in combination with furosemide, but not furosemide alone, reduced end-diastolic and end-systolic volumes, increased the left ventricular ejection fraction, and decreased (a) the plasma concentration of atrial natriuretic peptide, (b) the cardiac expression of V1aR, and (c) fibrosis in a model of heart failure following myocardial infarction (42,43). Similar results, as well as a …”

Section: Preclinical Studies In Heart Failurementioning

confidence: 99%

Vasopressin Receptor Antagonists, Heart Failure, and Polycystic Kidney Disease

Torres

2015

Annu. Rev. Med.

View full text Add to dashboard Cite

The synthesis of nonpeptide orally bioavailable vasopressin antagonists devoid of agonistic activity (vaptans) has made possible the selective blockade of vasopressin receptor subtypes for therapeutic purposes. Vaptans acting on the vasopressin V2 receptors (aquaretics) have attracted attention as a possible therapy for heart failure and polycystic kidney disease. Despite a solid rationale and encouraging preclinical testing, aquaretics have not improved clinical outcomes in randomized clinical trials for heart failure. Additional clinical trials with select population targets, more flexible dosing schedules, and possibly a different drug type or combination (balanced V1a/V2 receptor antagonism) may be warranted. Aquaretics are promising for the treatment of autosomal dominant polycystic kidney disease and have been approved in Japan for this indication. More studies are needed to better define their long-term safety and efficacy and optimize their utilization.

show abstract

Tolvaptan Attenuates Left Ventricular Fibrosis After Acute Myocardial Infarction in Rats

Cited by 9 publications

References 28 publications

Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure

Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure

Effectiveness of tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy for hepatoprotection and diuresis in a rat cirrhotic model

Vasopressin Receptor Antagonists, Heart Failure, and Polycystic Kidney Disease

Contact Info

Product

Resources

About