6-Hydroxydopamine mediated cardiotoxicity in rabbits.
Weekly injections of the catecholamine depleting agent 6-hydroxydopamine (6-OHDA) were used to denervate rabbit hearts chemically. Analyses of morphology and beta-adrenergic receptor density were made at 1, 2, and 4 weeks. Changes resulting from subacute and chronic inflammatory processes were evident by light microscopy after 1 week. At that time, electron microscopy revealed marked increases in collagen, large myocytic vacuolizations in myocytes, widened gap junctions, and myofibrillar degeneration and dropout. Receptor density was marginally increased at 2 weeks but was decreased (p less than .05) at 4 weeks (maximal [3H]dihydroalprenolol (DHA) binding in fmol/mg: 69.6 +/- 5.4 in controls vs 49.2 +/- 5.1 in 6-OHDA-treated animals). Basal, isoproterenol-stimulated and F- -stimulated adenylate cyclase activities were decreased in the 6-OHDA-treated group at 4 weeks. We conclude that administration of 6-OHDA may cause severe myocardial damage, and that this process may involve loss of some functional components of the cell membrane.
Lurie
K G
KG
Pathology Department, Stanford University Medical Center, California 94305.
Bristow
M R
MR
Minobe
W A
WA
Masek
M
M
Billingham
M E
ME
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D009202:Cardiomyopathies / Q000473:pathology; D004082:Dihydroalprenolol / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology* / Q000633:toxicity; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D011817:Rabbits; D013563:Sympathectomy, Chemical
D006892:Hydroxydopamines; D004082:Dihydroalprenolol; D016627:Oxidopamine; D000262:Adenylyl Cyclases; D009638:Norepinephrine