Tolvaptan attenuates left ventricular fibrosis after acute myocardial infarction in rats.
نویسندگان
چکیده
Tolvaptan, a non-peptide V2-receptor antagonist, is a newly developed diuretic agent. Recently, we reported that tolvaptan has diuretic as well as anti-inflammatory and anti-fibrotic actions in chronic heart failure. In this study, we investigated whether tolvaptan has a cardioprotective effect in acute heart failure after myocardial infarction (MI). After MI induction, rats were randomized into 6 groups as follows: vehicle group, group treated with 15 mg∙kg⁻¹∙day⁻¹ furosemide, 2 groups treated with 3 or 10 mg∙kg⁻¹∙day⁻¹ tolvaptan, and 2 groups treated with 15 mg∙kg⁻¹∙day⁻¹ furosemide combined with 3 or 10 mg∙kg⁻¹∙day⁻¹ tolvaptan. Each agent was administered for 2 weeks, and blood pressure levels and infarct sizes were similar in all MI groups. Lower left ventricular end-systolic volumes and greater improvement of left ventricular ejection fraction were observed in the tolvaptan-treated groups compared with the vehicle group. In contrast, furosemide alone did not improve them. Sirius red staining revealed that tolvaptan significantly repressed MI-induced interstitial fibrosis in the left ventricle. MI-induced mRNA expressions related to cardiac load, inflammation, and fibrosis were significantly attenuated in the combination group. The combination treatment also repressed MI-induced mineralocorticoid receptor expression. Tolvaptan, or combination of furosemide and tolvaptan, may improve cardiac function in acute MI.
منابع مشابه
Tolvaptan improves left ventricular dysfunction after myocardial infarction in rats.
BACKGROUND Arginine vasopressin, which promotes the reabsorption of renal water is increased in chronic heart failure. Here, we compared the effects of tolvaptan, a newly developed nonpeptide V(2) receptor antagonist, with those of furosemide, a loop diuretic, and a combination of these 2 agents in rats with left ventricular dysfunction after myocardial infarction (MI). METHODS AND RESULTS Af...
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عنوان ژورنال:
- Journal of pharmacological sciences
دوره 123 1 شماره
صفحات -
تاریخ انتشار 2013