An antioxidant role for calcium antagonists in the prevention of adrenaline mediated myocardial and endothelial damage.
OBJECTIVE
To investigate the mechanism of calcium antagonist mediated cytoprotection against the damaging effects of adrenaline in vivo on cardiac myocytes and human endothelial cells from the umbilical vein.


METHODS
Human endothelial cells cultured from the umbilical vein and isolated rat cardiac myocytes were treated with plasma from rats given adrenaline 30 minutes previously with pretreatment with calcium antagonists and without. The effect on indices of cell damage that suggest oxidation stress was determined.


RESULTS
Pretreatment of rats with calcium antagonists before adrenaline administration largely inhibited the cytotoxic effects of their plasma on the two target cells used. Plasma taken from animals not pretreated with calcium antagonists caused release of oxidised glutathione from cells, a fall in intra-cellular reduced glutathione concentration, a fall in ATP production, and release of angiotensin converting enzyme from the endothelial cells.


CONCLUSIONS
Calcium antagonists protect against the cardiotoxic effects of catecholamine by preventing the generation of plasma borne cytotoxic compounds, which are probably free radicals.
Noronha-Dutra
A A
AA
Department of Histopathology, Middlesex and University College, School of Medicine, London University.
Steen-Dutra
E M
EM
Woolf
N
N
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004837:Epinephrine / Q000009:adverse effects*; D005609:Free Radicals; D005978:Glutathione / Q000096:biosynthesis; D006321:Heart / Q000187:drug effects*; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D014471:Umbilical Veins / Q000473:pathology
D000975:Antioxidants; D002121:Calcium Channel Blockers; D005609:Free Radicals; D005978:Glutathione; D004837:Epinephrine