Effect of venotropic drugs on the respiratory activity of isolated mitochondria and in endothelial cells

1 Several drugs used in the treatment of chronic peripheral ischaemic and v enous diseases, i.e. aescine, Cycle 3, Ginkor Fort, hydroxyethylrutosides, naftidrofuryl, naphthoquinone and procyanidolic oligomers, were tested on t he mitochondrial respiratory activity. 2 The results show that all these drugs protected human endothelial cells a gainst the hypoxia-induced decrease in ATP content. In addition, they all i nduced a concentration-dependent increase in respiratory control ratio (RCR ) of liver mitochondria pre-incubated with the drugs for 60 min. 3 The drugs were divided into two groups according to their effects. The fi rst group (A), comprising aescine, Ginkor Fort, naftidrofuryl and naphthoqu inone, increased RCR by decreasing state 4 respiration rate. The second gro up of drugs (B), comprising hydroxyethylrutosides, procyanidolic oligomers and Cycle 3, increased RCR by increasing state 3 respiration rate. The drug s of group A were able to prevent the inhibition of complexes I and III res pectively by amytal and antimycin A while the first two drugs of group B in creased adenine nucleotide translocase activity. Cycle 3 inhibited the carb onylcyanide m-chlorophenyl hydrazone (mCCP)-induced uncoupling of mitochond rial respiration. None of these seven drugs could protect complexes IV and V, respectively, from inhibition by cyanide and oligomycin. 4 When tested on endothelial cells the drugs of group A, in contrast to gro up B, prevented the decrease in ATP content induced by amytal or antimycin A. 5 The present results suggest that the protective effects on mitochondrial respiration activity by these venotropic drugs may explain their protective effect on the cellular ATP content in ischaemic conditions and some of the ir beneficial therapeutic effect in chronic vascular diseases.