Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q10-enzymes by clinically used anti-hypertensive drugs

Res Commun Chem Pathol Pharmacol. 1975 Nov;12(3):533-40.

Abstract

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.

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Cattle
  • In Vitro Techniques
  • Mitochondria, Muscle / enzymology
  • Myocardium / enzymology
  • Myocardium / ultrastructure
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors
  • Succinate Dehydrogenase / antagonists & inhibitors
  • Ubiquinone / antagonists & inhibitors*

Substances

  • Antihypertensive Agents
  • Ubiquinone
  • Succinate Dehydrogenase
  • NADH, NADPH Oxidoreductases