Role of endogenous beta-adrenergic mechanism in the pathogenesis of spontaneous myocardial fibrosis in rats.
The role of endogenous beta-adrenergic activation in the pathogenesis of spontaneous myocardial fibrosis was investigated in male and female Sprague-Dawley (SD) rats. For the purpose of blocking endogenous beta-adrenergic activities, atenolol, a beta-adrenergic blocking a agent, was given at 20, 80 and 320 mg/kg/day mixed in the diet for 12 months. The transverse sections of the ventricles including the vulnerable region for spontaneous myocardial fibrosis was stained by Azan-Mallory method for collagen fibers and examined morphometrically, while being compared with the histological findings from standard hematoxylin-eosin procedure. The fibrosis was graded into 4 classes and compared between nontreated groups and treated groups of both sexes. Fibrous foci developed principally in the subendocardial myocardium. Atenolol failed to produce significant systemic toxic effects not only on weight gains and daily intakes of food but also on death rates. Atenolol did not prevent development of myocardial lesions in both sexes, whereas it significantly promoted fibrosis in the medium and high dose groups of male rats but not at any dose levels in female animals. It is suggested that endogenous beta-adrenergic activation plays no major role in the onset or development of spontaneous myocardial lesions, whereas the adrenergic system may probably control collagen synthesis in myocardial fibrosis.
Yoshimura
S
S
Hatano Research Institute, Food and Drug Safety Center, Hadano.
Hashimoto
K
K
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004719:Endomyocardial Fibrosis / Q000209:etiology* / Q000473:pathology; D005260:Female; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D001262:Atenolol