Isoproterenol and angiotensin I-converting enzyme in lung, left ventricle, and plasma during myocardial hypertrophy and fibrosis.
This study investigated whether long-term administration of isoproterenol (ISO) induces differential expression of angiotensin-converting enzyme (ACE) in lung, plasma, and left ventricle (LV) during development of left ventricular hypertrophy (LVH) and myocardial fibrosis. Male Sprague-Dawley rats (n = 7-9 per group) were treated with isoproterenol (ISO) 5 mg/kg per day for 10 days or saline and examined at 1, 15, and 33 days after the last injection. ISO stimulated the development of left ventricular hypertrophy (LVH); relative LV weight (mg LV 100/body weight), LV protein content, and LV beta-myosin heavy chain levels increased at day 1. LVH regressed at days 15 and 33. ISO also increased myocardial fibrosis (assessed by hydroxyproline content and morphometry) at days 15 and 33. There no were changes in arterial blood pressure. Long-term beta-adrenergic stimulation with ISO increased ACE expression in lung, LV, and plasma during development of LVH and myocardial fibrosis. However, time courses were markedly different. ISO stimulated a sustained increase in lung and plasma ACE activities, whereas ISO induced a high LV ACE. Plasma ACE activity paralleled lung ACE activity. LV ACE activity correlated with ACE mRNA levels and paralleled development of LVH. Our data suggest long-term beta-adrenergic stimulation induced a differential temporal expression of LV, lung, and plasma ACE in rat during development of LVH and myocardial fibrosis.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Olivos 1007, Santiago, Chile.
María Paz
MP
Ocaranza
Guillermo
G
Díaz-Araya
Mario
M
Chiong
David
D
Muñoz
Juan Pablo
JP
Riveros
Roberto
R
Ebensperger
Sebastián
S
Sabat
Pablo
P
Irarrázaval
Jorge E
JE
Jalil
Sergio
S
Lavandero
D000818:Animals; D002316:Cardiotonic Agents / Q000633:toxicity; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007545:Isoproterenol / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects
D002316:Cardiotonic Agents; D007703:Peptidyl-Dipeptidase A; D007545:Isoproterenol