MECHANISM OF ENDOTHELIUM-DEPENDENT RELAXATION INDUCED BY THROMBIN IN THE PIG CORONARY-ARTERY

The mechanism of thrombin-induced endothelium-dependent relaxation was investigated using fura-2 front-surface fluorometry. Thrombin induced an endothelium-dependent relaxation during U46619-induced contraction s in pig coronary arterial strips. The relaxation consisted of two com ponents: the early phasic component with a transient decrease in [Ca2](i) of smooth muscle and the subsequent sustained tonic component wit hout [Ca2+]i decrease. The phasic relaxation was inhibited by a combin ation of N-omega-nitro-L-arginine and K+-depolarization, while the ton ic component was inhibited by either indomethacin or K+-depolarization . Thrombin induced a transient [Ca2+](i) increase and nitric oxide (NO ) production in pig aortic valvular endothelial cells, which expressed NO synthase as determined by reverse transcription and polymerase cha in reaction. Thus, it was concluded that NO and hyperpolarizing factor were involved in the phasic component of thrombin-induced relaxation and that hyperpolarizing factor and prostacyclin were involved in the tonic component. (C) 1998 Elsevier Science B.V. All rights reserved.