title: Possible roles of cardiac chymase after myocardial infarction in hamster hearts.
abstract: The significance of cardiac chymase after myocardial infarction (MI) was evaluated using a hamster model of MI. At 1, 3, 7, 14, 28 and 56 days after MI, tissues were removed for measurements of angiotensin-converting enzyme (ACE) and chymase activities. The mean infarct size 3 days after left coronary artery ligation was 47.3 +/- 5.9% of the left ventricle circumference. The ratio of left ventricle weight to body weight was significantly increased from 3 days after MI. The level of plasma renin activity in the MI hamsters was significantly increased at the early phase of MI (1-3 days), while no significant changes in plasma ACE activity were observed. The ACE activity in the infarcted left ventricle was significantly increased starting from 3 days after MI and this increase was sustained up to 28 days. The chymase activity in the infarcted left ventricle was significantly increased starting from 1 day after MI and this increase was sustained up to 56 days. The number of chymase-positive mast cells in the infarcted left ventricle was significantly higher than in the sham group 3 and 7 days after operation. Treatment with an angiotensin (Ang) II type 1 receptor antagonist (candesartan cilexetil, 10 mg/kg per day) starting 3 days before the induction of MI significantly reduced the mortality rate during 14 days of observation following MI, whereas treatment with an ACE inhibitor (lisinopril, 20 mg/kg per day) did not. A significant improvement in hemodynamics (maximal negative and positive rates of pressure development, left ventricular systolic pressure and end-diastolic pressure, mean arterial blood pressure) was observed by the treatment with candesartan cilexetil, but not with lisinopril, 3 and 14 days after MI. These results suggested that Ang II produced by chymase may participate in the pathophysiologic state after MI in hamsters.
authors.affiliation: Department of Pharmacology, Osaka Medical College, Takatsuki City, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Jin
authors.forename: S
authors.initials: S
authors.lastname: Takai
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Yao
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D053818:Chymases; D006224:Cricetinae; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D009203:Myocardial Infarction / Q000201:enzymology* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011945:Receptors, Angiotensin / Q000502:physiology; D012083:Renin / Q000097:blood; D012697:Serine Endopeptidases / Q000096:biosynthesis*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases; D012083:Renin