Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q10-enzymes by clinically used anti-hypertensive drugs.
Background data revealed that some American and Japanese patients with essential hypertension, including many who were not being treated with any anti-hypertensive drug, had a deficiency of coenzyme Q10. Eight clinically used anti-hypertensive drugs have now been tested for inhibition of two mitochondrial coenzyme Q10-enzymes of heart tissue, succinoxidase and NADH-oxidase. Diazoxide and propranolol significantly inhibited the CoQ10-succinoxidase and CoQ10-NADH-oxidase, respectively. Metoprolol did not inhibit succinoxidase, and was one-fourth as active as propranolol for inhibition of NADH-oxidase. Hydrochlorothiazide, hydralazine, ans clonidine also inhibited CoQ10-NADH-oxidase. Reserpine did not inhibit either CoQ10-enzyme, and methyldopa was a very eak inhibitor of succinoxidase. The internationally recognized clinical side-effects of propranolol may be due, in part, to inhibition of CoQ10-enzymes which are indispensable in the bioenergetics of cardiac function. A pre-existing deficiency of coenzyme Q10 in the myocardium of hypertensive patients could be augmented by subsequent treatment with propranolol, possibly to the "life-threatening" state described by others.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002417:Cattle; D066298:In Vitro Techniques; D008931:Mitochondria, Muscle / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology / Q000648:ultrastructure; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D014451:Ubiquinone / Q000037:antagonists & inhibitors*
D000959:Antihypertensive Agents; D014451:Ubiquinone; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases