Tolvaptan Improves Left Ventricular Dysfunction after Myocardial Infarction in Rats

作者：Yamazaki Takanori; Izumi Yasukatsu^*; Nakamura Yasuhiro; Yamashita Naoto; Fujiki Hiroyuki; Osada Oka Mayuko; Shiota Masayuki; Hanatani Akihisa; Shimada Kenei; Iwao Hiroshi; Yoshiyama Minoru

来源：Circulation-Heart Failure, 2012, 5(6): 794-802.

DOI：10.1161/CIRCHEARTFAILURE.112.968750

• arginine vasopressin
• diuretic
• echocardiography
• left ventricular dysfunction
• tolvaptan

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). %26lt;br%26gt;Methods and Results-After 10 weeks of MI induction, the rats were separated them into the following 6 groups adjusted to the infarct size: a vehicle group, a group treated with 15 mg.kg(-1).day(-1) of furosemide, 2 groups treated with 3 or 10 mg.kg(-1).day(-1) of tolvaptan; and 2 groups treated with 15 mg.kg(-1).day(-1) of furosemide plus 3 or 10 mg.kg(-1).day(-1) tolvaptan. Each treatment agent was administered for 4 weeks, and all groups had similar blood pressure levels and infarct size. The tolvaptan-treated groups were found to have lower levels of left ventricular end-diastolic and systolic cardiac volumes than the vehicle group did. Furthermore, the improvement in the ejection fraction in the tolvaptan-treated groups was significantly greater than those in the vehicle group. ED-1 immunostaining and Sirius red staining revealed that tolvaptan significantly repressed MI-induced macrophage infiltration and interstitial fibrosis in the left ventricle, respectively. Tolvaptan attenuated the MI-induced mRNA expressions of atrial and brain natriuretic peptides, monocyte chemotactic protein-1, transforming growth factor-beta 1, arginine vasopressin V-1a receptor, and endothelin-1 in the marginal infarct region. %26lt;br%26gt;Conclusions-Tolvaptan may improve cardiac dysfunction after MI, which is partially mediated by the suppression of V-1a receptor, neurohumoral activation and inflammation. (Circ Heart Fail. 2012;5:794-802.)

• 出版日期2012-11