Improvement of endocardial and vascular endothelial function on myocardial performance by captopril treatment in postinfarct rat hearts.
Background-Endocardial (EE) and myocardial capillary vascular endothelial (myocap VE) cells have been shown to modulate the contractile characteristics of myocardium in a calcium-dependent manner. We evaluated the endothelial-myocardial interaction in the rat postinfarction myocardial infarction (MI) model and the effects of captopril. Methods and Results-Wistar rats were divided into 4 groups treated for 4 weeks: (1) control; (2) infarcted controls (left anterior coronary artery ligation); (3) infarcted+captopril 2 g/L in drinking water; and (4) infarct+captopril+triton intracoronary injection. Coronary VE function was evaluated by infusion of serotonin in Langendorff preparations (n=31), and the myocardial contractile characteristics were investigated by use of isolated papillary muscles (n=44). Cardiac mRNA for endothelial constitutive nitric oxide synthase (ecNOS) was measured, and its cellular location was evaluated by immunohistochemistry. Serotonin-induced increase in coronary flow was decreased in infarct controls compared with controls (4.6% versus 53.4%, P<0.01) but not in the 2 infarct+captopril groups. Intracoronary triton injection decreased serotonin-induced coronary flow in the infarct+captopril+triton group. All MI groups had decreased total tension in isolated papillary muscles. EE removal by triton immersion decreased total tension in all groups except for infarct controls (3.3 versus 3.2 g/mm(2)). Cardiac ecNOS mRNA decreased in the control infarct group but remained normal in the infarct+captopril group. Conclusions-Chronic postinfarction endothelium-induced coronary vasodilatation is impaired, and both EE and myocap VE dysfunction contribute to myocardial depression. Captopril use prevents these abnormalities and the reduction of cardiac ecNOS mRNA.
Qi
X L
XL
Department of Medicine, Montreal Heart Institute, Montreal, Quebec , Canada.
Stewart
D J
DJ
Gosselin
H
H
Azad
A
A
Picard
P
P
Andries
L
L
Sys
S U
SU
Brutsaert
D L
DL
Rouleau
J L
JL
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002196:Capillaries / Q000502:physiology; D002216:Captopril / Q000494:pharmacology*; D003331:Coronary Vessels / Q000503:physiopathology*; D004699:Endocardium / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects*; D007150:Immunohistochemistry; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000032:analysis; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D012701:Serotonin; D002216:Captopril; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat