Understanding the nature and role of endothelium-derived hyperpolarizing factor appears to be crucial in the quest for improved treatments for hypertension, diabetes, ischemia-reperfusion and other vascular disorders.
EDHF 2000 comprises the proceedings of the Third International Symposium on endothelium-dependent hyperpolarizations. The first two meetings established a role for EDHF and other chemical factors involved in endothelium-dependent hyperpolarizations. These proceedings focus upon the role of gap junctions in cardiovascular responses and investigate the chemical identity of EDHF. Additional chapters on Physiology, Hormonal Modulation and Pathological Changes are also included.
EDHF 2000 will be of interest not only to physiologists and pharmacologists puzzled by the complexity of the interactions between the endothelium and underlying vascular smooth muscle cells, but also clinical researchers and physicians treating patients with cardiovascular diseases.
1. What do gap junctions do anyway? 2. Cardiovascular gap junctions: Functional Diversity, complementation and specialization of connexins 3. Endothelium and smooth muscle pathways for conduction along resistance microvessels 4. Membrane potential and calcium responses evoked by acetylcholine in submucosal arterioles of the guinea-pig small intestine 5. The effects of ouabain, 18a-glycyrrhetinic acid and connexin-mimetic peptides on intercellular communication in cells expressing a Cx43-GFP chimeric protein 6. Role of gap junctions in endothelium-dependent hyperpolarizations 7. Heterogeneity of EDHF-type relaxations of rabbit and rat arteries analysed with peptides homologous to the extracelluar loops of connexins 37, 40 and 43 8. Myoendothelial and circumferential spread of endothelium-dependent hyperpolarization in coronary arteries 9. Direct myoendothelial contact in human pulmonary microvessels 10. Role of gap junctional communication in EDHF-mediated responses and mechanisms of K-induced dilatations 11. Comparison of alpha and beta isoforms of glycyrrhetinic acid and carbenoxolone as inhibitors of EDHF-type relaxation 12. Inhibitory effect of 18-beta-glycyrrhetinic acid on the relaxation induced by acetylcholine in the rat aorta 13. A central role for endothelial cell potassium channels in EDHF-mediated responses 14. Could the EDHF be K in porcine coronary arteries? 15. Nitro-L-arginine/indomethacin-resistant relaxations to acetylcholine in small gastric arteries of the rat: Effect of ouabain plus Ba2+ and relation to potassium ions 16. Effects of barium, ouabain and K+ on the resting membrane potential and endothelium-dependent responses in rat arteries 17. EDHF and potassium: Blockade of chloride channels reveals relaxations of rat mesenteric artery to potassium 18. Cytochrome P450 2C is a source of EDHF and reactive oxygen species in the porcine coronary artery 19. Cortisol increases EDHF-mediated relaxations in porcine coronary artery 19. Cortisol increases EDHF-mediated relaxations in porcine coronary arteries and up-regulates the expression of cytochrome P450 2C9 20. An arachidonic acid metabolite(s) produced by the endothelial cytochrome P450 isoform, CYP3A4, relaxes the lingual artery of the monkey via K+ channel opening 21. EDHF-mediated responses induced by bradykinin in the porcine coronary artery 22. Epoxyeicosatrienoic acid release mediates nitric oxide-independent dilatation of rat mesenteric vessels 23. Epoxyeicosatrienoic acid and endothelium-dependent hyperpolarization in porcine coronary arteries 24. Lipoxygenase-derived metabolites of arachidonic acid are not involved in the endothelium-dependent hyperpolarization to acetylcholine in the carotid artery of the guinea-pig 25. Cytochrome P450 isoforms in the brain encode cell specific hyperpolarizing factors with a common mechanism of action 26. Expression of recombinant cytochrome P450 epoxygenase in rat brain 27. Identification of 11, 12, 15-trihydroxyeicosatrienoic acid as the mediator of acetylcholine- and arachidonic acid-induced relaxations in the rabbit aorta 28. Identification of hydrogen peroxide as an endothelium-derived hyperpolarizing factor in mice 29. Components of the potassium currents underlying the actions of endothelium- derived hyperpolarizing factor in arterioles 30. Evidence for relaxation to endothelium-derived hyperpolarizing factor (EDHF) in isolated small mesenteric arteries of the mouse 31. Pharmacological characterization of potassium channels in intact mesenteric arteries and single smooth muscle cells from eNOS-/- and +/+ mice 32. EDHF, which is not NO, is a major endothelium-dependent vasodilator in mice 33. Prostacyclin and iloprost in the isolated carotid artery of the guinea pig 34. Role of charybdotoxin/apamin sensitive K+ Ca channels in pulsatile perfusion- mediated coronary vasodilatation in vivo 35. Essential role of estrogen in the EDHF-mediated responses of mesenteric arteries from middle-aged female rats: Possible contribution of gap junctional protein connexin 43 36. Endothelium-derived hyperpolarizing factor (EDHF) and utero-feto-placental circulation in the rat 37. Endothelium-derived hyperpolarizing factor maintains a normal relaxation to bradykinin despite impairment of the nitric oxide pathway in porcine coronary arteries with regenerated endothelium 38. Mechanisms underlying the vasodilatation caused by bradykinin in essential hypertensive patients 39. Influence of diabetes on endothelium-dependent responses in mesenteric and femoral arteries of rats 40. Folate restores the NO synthase- and cyclooxygenase-resistant renal vasodilator response to acetylcholine in diabetes 41. Resistance of EDHF-mediated relaxations to oxidative stress in human radial arteries 42. Critical limb ischemia results in different types of endothelial dysfunction depending on the vascular bed studied 43. Potentiated EDHF-mediated dilatations in the rat middle cerebral artery following ischemia/reperfusion 44. The EDHF-dependent but not the NO-dependent component of the acetylcholine-induced relaxation of the rabbit aorta is resistant to ionized radiation 45. Inhibition of converting enzyme prevents the age-related decline in endothelium-dependent hyperpolarization 46. Effects of a converting enzyme inhibitor, an AT1-receptor antagonist and their combination on endothelial dysfunction in hypertension 47. EDHF: Gap junction or chemical? And many other questions