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 effiux 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.

Enhanced role for the opening of potassium channels in relaxant responses to acetylcholine after myocardial ischaemia and reperfusion in dog coronary arteries

“…Bolotina et al, (1994) also demonstrated that relaxation to NO was blocked by charybdotoxin, a speci®c inhibitor of calciumdependent potassium channels, in rabbit aortic smooth muscle cells. By contrast other studies reported that endotheliumdependent relaxation but not endothelium-dependent hyperpolarization was inhibited by methylene blue or Hb in rat (Chen et al, 1988) or rabbit arteries (Huang et al, 1988) indicating a factor other than NO caused hyperpolarization. Thus, both NO and EDHF have been suggested to open the potassium channels leading to hyperpolarization in response to ACh.…”

Endothelium‐dependent hyperpolarization and intercellular electrical coupling in guinea‐pig mesenteric arterioles

“…Since Chen et al (1988) reported endothelium-dependent hyperpolarization of vascular smooth muscle, this phenomenon has been thought to be produced by an unidentified humoral substance (EDHF) released from vascular endothelium (Chen et al 1991). In the presence of 18â_glycyrrhetinic acid, electrical coupling between cells was effectively blocked and the membrane potential of individual cells could be well clamped while all cell types remained located within a multicellular preparation.…”

Dominant role of an endothelium‐derived hyperpolarizing factor (EDHF)‐like vasodilator in the ciliary vascular bed of the bovine isolated perfused eye

“…In systemic arteries, the vascular endothelium plays a major role in the regulation of vasomotor tone through the release of the vasodilators, nitric oxide (Moncada et al, 1991), prostacyclin (Moncada & Vane, 1979) and the putative endotheliumderived hyperpolarizing factor (EDHF, Chen et al, 1988). There is now compelling evidence to support the view that endothelium-derived nitric oxide is an important mediator of vasomotor tone in the eye (for review see Koss, 1999).…”