The antihypertensive drug carvedilol inhibits the activity of mitochondrial NADH-ubiquinone oxidoreductase.
A study is presented on the interaction of carvedilol with mitochondria isolated from several rat organs. It is shown that carvedilol causes a moderate uncoupling effect under non phosphorylating succinate supported respiration of intact mitochondria, as well as a marked inhibition of coupled respiration with NAD-dependent substrates. The inhibitory effect was also found in the bovine heart purified Complex I as well as in experiments with mitochondrial particles, where the individual redox segments of the respiratory chain were analysed. It is also shown that carvedilol, though exhibiting an intrinsic scavenger activity, caused reactive oxygen species to be produced as a consequence of its inhibitory effect on the steady-state respiration. Under these conditions the pro-oxidant activity of carvedilol appears to prevail over its scavenging activity, and a net generation of ROS is promoted.
Cocco
Tiziana
T
Department of Medical Biochemistry and Biology, University of Bari, Italy.
Cutecchia
Giuseppe
G
Montedoro
Grazia
G
Lorusso
Michele
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D042967:Electron Transport Complex I; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D002227:Carbazoles; D004791:Enzyme Inhibitors; D024101:Mitochondrial Proteins; D011412:Propanolamines; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D000077261:Carvedilol; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I