Influence of trimetazidine, an antianginal drug, on isolated dog arteries and veins.

In helical strips of dog coronary, mesenteric, renal, femoral and basilar arteries contracted with prostaglandin F2 alpha, trimetazidine produced a dose-related relaxation, which was not influenced by treatment with propranolol, atropine, cimetidine, aminophylline and aspirin. Relaxations induced by trimetazidine of strips of large and small coronary arteries did not differ, while those of large artery strips induced by nitroglycerin were significantly greater. Mesenteric vein strips responded with a greater relaxation to trimetazidine than mesenteric artery strips, while the vein and artery strips relaxed in response to nitroglycerin to a similar extent. Contractile responses to transmural stimulation and norepinephrine of mesenteric vein strips were attenuated by trimetazidine to a greater extent than those of artery strips. However, trimetazidine did not protect alpha-adrenoceptors from persistent blockade by phenoxybenzamine. Treatment with high concentrations of trimetazidine attenuated the relaxant response to isoproterenol of coronary arteries and the contractile response to Ca++ of the arteries exposed to Ca++-free media and depolarized by excess K+. It may be concluded that trimetazidine preferentially relaxes venous muscle and reduces contractile responses of veins to activation of sympathetic nerves, thereby reducing venous return or preload of the heart.