当前位置： SCI文献检索 > JOURNAL OF CARDIOVASCULAR PHARMACOLOGY期刊下所有文献 > Chymase inhibitor improves survival in hamsters with myocardial infarction.

Chymase inhibitor improves survival in hamsters with myocardial infarction.

Abstract：

:The purpose of the present study was to assess the effects of chronic treatment with an orally active chymase inhibitor, 4-[1-(naphthylmethyl)benzimidazol-2-ylthio]butanoic acid (TEI-E548), in a hamster myocardial infarction model. In the first experiment, after confirming the biochemical inhibitory action of TEI-E548 on human and hamster chymases (Ki = 6.2 and 30.6 nM, respectively), the biological action of TEI-E548 in vivo was assessed by the inhibition of hamster chymase-induced microvascular leakage. In the second experiment, myocardial infarction was produced by coronary artery ligation in male Syrian hamsters. TEI-E548 (0.1% containing chow) was given 24 h after surgery and continued for 3 or 5 weeks, while the control and sham-operated groups were fed a standard chow. The survival rate was assessed in each group. At the end of each study period, blood pressure was measured at the left hind-limb, the heart rate and cardiac function were measured by echocardiography, the end-diastolic pressure by a direct catheterization, and organ weights and biochemical parameters, including plasma renin and angiotensin-converting enzyme activities and plasma angiotensin I and angiotensin II concentrations, were measured. In the first experiment, a standard chow containing 0.1% TEI-E548 completely inhibited the hamster chymase-induced microvascular leakage. In the second experiment, TEI-E548 treatment significantly increased the survival rate (37% versus control), and attenuated cardiac hypertrophy (13% versus control) and end-diastolic left ventricular pressure (34% versus control), but it did not decrease the infarction size nor improve the ejection fraction. The plasma angiotensin II concentration post-myocardial infarction was significantly suppressed by TEI-E548 throughout the study period. We conclude that TEI-E548 is an orally active useful chymase inhibitor and improves survival and cardiac hypertrophy of the post-myocardial infarction hamster.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Hoshino F,Urata H,Inoue Y,Saito Y,Yahiro E,Ideishi M,Arakawa K,Saku K

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

S11-8

eissn

0160-2446

issn

1533-4023

journal_volume

41 Suppl 1

pub_type

杂志文章

在线工具

Chymase inhibitor improves survival in hamsters with myocardial infarction.