Acetylcholine releases endothelium‐derived hyperpolarizing factor and EDRF from rat blood vessels

Abstract

1 The effects of haemoglobin and methylene blue on the acetylcholine (ACh)-induced electrical and mechanical responses of smooth muscle cells were investigated in rat aorta and rat main pulmonary artery. 2 When the endothelium was intact, ACh induced a transient hyperpolarization and sustained relaxation of tissues precontracted with noradrenaline. Both hyperpolarization and relaxation were absent in preparations without endothelium. 3 Haemoglobin and methylene blue inhibited the ACh-induced relaxation, but not the transient hyperpolarization. 4 In aorta with an intact endothelium, ACh produced an increase in both the rate of ⁸⁶Rb efflux and tissue cyclic GMP levels. The changes in ion flux were unaffected by either haemoglobin or methylene blue in concentrations which almost abolished the increase in cyclic GMP concentrations. 5 In arteries with an intact endothelium, indomethacin had no effect on the ACh-induced electrical and mechanical responses or on the increase in ⁸⁶Rb efflux and tissue cyclic GMP levels. 6 It is concluded that in the rat aorta and rat main pulmonary artery, ACh releases two different substances, an endothelium-derived relaxing factor (EDRF) and a hyperpolarizing factor (EDHF), from the endothelial cells. Neither substance appears to be derived from a pathway dependent on cyclo-oxygenase. EDHF seems to play a minor role in the relaxation of noradrenaline-induced contractions.