Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats.
The long-term administration of N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, produces coronary vascular remodeling and myocardial hypertrophy in animals. This study used a rat model to investigate the role of angiotensin I converting enzyme (ACE) in the pathogenesis of such changes. We studied the following groups, all of which received drug treatment in their drinking water: untreated controls, and those administered L-NAME, L-NAME, and an ACE inhibitor (ACEI), and L-NAME and hydralazine. Cardiovascular structural changes and tissue ACE activities were evaluated after the first, fourth, and eighth week of treatment. In rats treated with L-NAME alone, vascular remodeling was evident at the fourth and eighth week, and myocardial hypertrophy was present at the eighth week of treatment. The vascular and myocardial remodeling were characterized by increased tissue ACE activities and immunodetectable ACE in those tissues. These changes were markedly reduced by ACEI, but not by hydralazine treatment. Increased local ACE expression may thus be important in the pathogenesis of cardiovascular remodeling in this model.
Takemoto
M
M
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.
Egashira
K
K
Usui
M
M
Numaguchi
K
K
Tomita
H
H
Tsutsui
H
H
Shimokawa
H
H
Sueishi
K
K
Takeshita
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D006332:Cardiomegaly; D003331:Coronary Vessels / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005355:Fibrosis; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D014018:Tissue Distribution
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A; D019331:NG-Nitroarginine Methyl Ester