endothelium dependent relaxing factors


Summary: Paracrine substances produced by the VASCULAR ENDOTHELIUM with VASCULAR SMOOTH MUSCLE relaxation (VASODILATION) activities. Several factors have been identified, including NITRIC OXIDE and PROSTACYCLIN.

Top Publications

  1. Evora P, Pearson P, Rodrigues A, Viaro F, Schaff H. Effect of arginine vasopressin on the canine epicardial coronary artery: experiments on V1-receptor-mediated production of nitric oxide. Arq Bras Cardiol. 2003;80:483-94 pubmed
    ..05). Vasopressin acts through V1 endothelial receptors to stimulate nitric oxide release from L-arginine. ..
  2. Queiroz R, Ramos E, Alves Do Prado W. 4-Aminopyridine inhibits the neuromuscular effects of nitric oxide and 8-Br-cGMP. Braz J Med Biol Res. 2003;36:937-41 pubmed
    ..Therefore, the presynaptic effects induced by NO seem to depend on indirect interactions with K+ channels. ..
  3. Wimalasundera R, Fexby S, Regan L, Thom S, Hughes A. Effect of tumour necrosis factor-alpha and interleukin 1beta on endothelium-dependent relaxation in rat mesenteric resistance arteries in vitro. Br J Pharmacol. 2003;138:1285-94 pubmed
    ..This mechanism could contribute to the endothelial dysfunction seen in situations where TNF is elevated, such as pre-eclampsia. ..
  4. Travadi J, Patole S. Phosphodiesterase inhibitors for persistent pulmonary hypertension of the newborn: a review. Pediatr Pulmonol. 2003;36:529-35 pubmed
    ..The need for randomized-controlled trials to determine the safety, efficacy, and long-term outcome following treatment with sildenafil in PPHN is emphasized. ..
  5. Tottrup A, Kraglund K. Endothelium-dependent responses in small human mesenteric arteries. Physiol Res. 2004;53:255-63 pubmed
    ..Synthesis of both EDNO and EDHF seem important for these relaxations, whereas prostaglandins seem to be of minor importance. ..
  6. Lakshminrusimha S, Russell J, Gugino S, Ryan R, Mathew B, Nielsen L, et al. Adjacent bronchus attenuates pulmonary arterial contractility. Am J Physiol Lung Cell Mol Physiol. 2006;291:L473-8 pubmed
    ..NO gas relaxed PA when administered on the endothelial side only. We speculate that BrDRF is a diffusible factor that crosses the adventitia and stimulates production of NO within the PA. ..
  7. Okamura T. [EDRF]. Nihon Rinsho. 2006;64 Suppl 5:244-8 pubmed
  8. Pribylov S, Konoplia A, Sirotkin S. [Endothelial dysfunction mediators in patients with chronic cor pulmonale]. Klin Med (Mosk). 2006;84:20-4 pubmed
    ..Data on endothelium-dependent vasoactive mediators are presented in the article. ..
  9. Stefan C, Dumitrica D, Ardeleanu C. [The future started: nitric oxide in glaucoma]. Oftalmologia. 2007;51:89-94 pubmed

More Information


  1. Pearce W, Williams J, White C, Lincoln T. Effects of chronic hypoxia on soluble guanylate cyclase activity in fetal and adult ovine cerebral arteries. J Appl Physiol (1985). 2009;107:192-9 pubmed publisher
  2. Halvey E, Vernon J, Roy B, Garthwaite J. Mechanisms of activity-dependent plasticity in cellular nitric oxide-cGMP signaling. J Biol Chem. 2009;284:25630-41 pubmed publisher
    ..A kinetic model explicitly describing the complex interplay between NO concentration, cGMP synthesis, PDE5 activation, and the resulting cGMP accumulation successfully simulated the present and previous data. ..
  3. Zeng Z, Zhang Z, Luo B, He W, Liang L, He C, et al. The functional changes of the perivascular adipose tissue in spontaneously hypertensive rats and the effects of atorvastatin therapy. Clin Exp Hypertens. 2009;31:355-63 pubmed
    ..These results provide an insight into the pathological mechanisms of hypertension development, and indicate that the PVAT may be a potential new target for the hypertensive therapy. ..
  4. Wang J, Li Z. [Endothelium derived relaxing factor and its effect on vascular disease]. Wei Sheng Yan Jiu. 2003;32:508-10 pubmed
    ..As the provider of EDRF, Nitryl vascular relaxation substance could remedy EDRF and might play an important role in clinical therapy and prevention of human vascular disease. ..
  5. Taddei S, Ghiadoni L, Virdis A, Versari D, Salvetti A. Mechanisms of endothelial dysfunction: clinical significance and preventive non-pharmacological therapeutic strategies. Curr Pharm Des. 2003;9:2385-402 pubmed
    ..It is worth noting that most of non-pharmacological measures act by preventing or reducing oxidative stress. ..
  6. Witcher D, Sakai N, Williams B, Rahimian R, Anderson L. Gender differences in the effects of streptozotocin-induced diabetes on parasympathetic vasodilatation in the rat submandibular gland. Arch Oral Biol. 2010;55:745-53 pubmed publisher
    ..However, in males diabetes predominantly impairs PGI2- and NO-dependent vasodilatation, whereas in females the contribution of EDHF-mediated pathways are affected and NO-dependent vasodilatation is preferentially maintained. ..
  7. Bertuglia S, Veronese F, Pasut G. Polyethylene glycol and a novel developed polyethylene glycol-nitric oxide normalize arteriolar response and oxidative stress in ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2006;291:H1536-44 pubmed
    ..In conclusion, PEG-NO shows promise as a compound that protects microvascular perfusion by normalizing the balance between NO level and excessive production of free radicals in endothelial cells during I/R injury. ..
  8. Hermans G, Wilmer A, Knockaert D, Bobbaers H. Acute intracardiac right-to-left shunt in a patient with acute respiratory distress syndrome and shock successfully treated with nitric oxide. Br J Anaesth. 2006;96:268-9 pubmed
  9. He G. Endothelial function related to vascular tone in cardiac surgery. Heart Lung Circ. 2005;14:13-8 pubmed
    ..A number of methods have been suggested to protect endothelial function in either coronary circulation or in coronary artery bypass grafts during cardiac surgery but further investigations in this field are warranted. ..
  10. Thérèse P. Persistent pulmonary hypertension of the newborn. Paediatr Respir Rev. 2006;7 Suppl 1:S175-6 pubmed
    ..PPHN is in fact a variety of disorders that have a common presentation. Some of the pathophysiological mechanisms and the therapeutic approaches are discussed below. ..
  11. Rodrigues A, Evora P, Maruo A, Schaff H. [Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries]. Arq Bras Cardiol. 2005;84:251-5 pubmed
    ..The results obtained indicate that vasodilation promoted by amiodarone in canine coronary arteries is mainly caused by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors. ..
  12. Yousif M. Histamine-induced vasodilation in the perfused kidney of STZ-diabetic rats: role of EDNO and EDHF. Pharmacol Res. 2005;51:515-21 pubmed
    ..Results have also indicated that the EDHF component of histamine-induced vasodilatation was mediated through Ca2+ -activated K+ channels in perfused kidney preparations from both control and diabetic rats. ..
  13. Yang A, Chen H. Chronic exercise reduces adhesion molecules/iNOS expression and partially reverses vascular responsiveness in hypercholesterolemic rabbit aortae. Atherosclerosis. 2003;169:11-7 pubmed
    ..We conclude that exercise training decreases the expression of adhesion molecules and iNOS, and ameliorates the severe vascular dysfunction induced by high cholesterol feeding. ..
  14. Liu V, Huang P. Cardiovascular roles of nitric oxide: a review of insights from nitric oxide synthase gene disrupted mice. Cardiovasc Res. 2008;77:19-29 pubmed
    ..Mice lacking the inducible isoform show reduced hypotension to septic shock. Together, NOS gene knockout mice have been useful tools that complement our other approaches to studying the multiple roles of NO in the cardiovascular system. ..
  15. Goto M, Mochizuki S. Plasma detection of NO by a catheter. Med Biol Eng Comput. 2008;46:509-16 pubmed publisher
    ..In this article, the measurement of plasma NO concentration using a newly developed catheter-type NO sensor will be described. ..
  16. Seppey D, Sauser R, Koenigsberger M, Beny J, Meister J. Does the endothelium abolish or promote arterial vasomotion in rat mesenteric arteries? Explanations for the seemingly contradictory effects. J Vasc Res. 2008;45:416-26 pubmed publisher
    ..Our findings clarify the role of the endothelium on vasomotion and reconcile the seemingly contradictory observations reported in the literature. ..
  17. Vaschetto R, Kuiper J, Musters R, Eringa E, Della Corte F, Murthy K, et al. Renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of VILI: the role of the peroxynitrite-PARP pathway. Crit Care. 2010;14:R45 pubmed publisher
  18. Shimokawa H. Hydrogen peroxide as an endothelium-derived hyperpolarizing factor. Pflugers Arch. 2010;459:915-22 pubmed publisher
    ..In this review, we summarize our current knowledge on H(2)O(2)/EDHF regarding its identification and mechanisms of synthesis and actions. ..
  19. Zhang D, Gauthier K, Falck J, Siddam A, Campbell W. Steroid-producing cells regulate arterial tone of adrenal cortical arteries. Endocrinology. 2007;148:3569-76 pubmed
    ..We conclude that ZG cells release EETs and this release is stimulated by ACTH. Interaction of endocrine and vascular cells represents a mechanism for regulating adrenal blood flow and couples steroidogenesis to increased blood flow. ..
  20. Lewis S, Travis M, Hashmi Hill M, Sandock K, Robertson T, Bates J. Differential effects of ouabain on the vasodilator actions of nitric oxide and S-nitrosothiols in vivo: relevance to the identity of EDRF/EDHF. Vascul Pharmacol. 2006;45:383-94 pubmed
  21. Chua Y, Evora P, Celotto A, Pearson P, Discigil B, Schaff H. Adaptation of bioassay to detect endothelium-derived relaxing factors from the canine atrial endocardium. Rev Bras Cir Cardiovasc. 2009;24:225-32 pubmed
    ..The ability of the endocardial endothelium to produce these factors could play an important role in preventing thrombus formation in the cardiac chambers. ..
  22. Ho W, Hiley C. Vasodilator actions of abnormal-cannabidiol in rat isolated small mesenteric artery. Br J Pharmacol. 2003;138:1320-32 pubmed
    ..It also causes endothelium-independent, SR 141716A-insensitive, relaxation by inhibiting Ca(2+) entry through voltage-gated Ca(2+) channels. ..
  23. Gschwend S, Henning R, Pinto Y, de Zeeuw D, van Gilst W, Buikema H. Myogenic constriction is increased in mesenteric resistance arteries from rats with chronic heart failure: instantaneous counteraction by acute AT1 receptor blockade. Br J Pharmacol. 2003;139:1317-25 pubmed
  24. Gauthier K, Edwards E, Falck J, Reddy D, Campbell W. 14,15-epoxyeicosatrienoic acid represents a transferable endothelium-dependent relaxing factor in bovine coronary arteries. Hypertension. 2005;45:666-71 pubmed
    ..14,15-EEZE blocked the donor artery, endothelium-dependent, bradykinin-induced relaxations, and attenuated relaxations to 14,15-EET. These results suggest that EETs are transferable EDHFs in coronary arteries. ..
  25. Yamane T, Matsumoto T, Nakae I, Takashima H, Tarutani Y, Tamaki S, et al. Impact of paraoxonase polymorphism (Q192R) on endothelial function in intact coronary circulation. Hypertens Res. 2006;29:417-22 pubmed
    ..In conclusion, as estimated by BK and ACh testing, our findings suggest that PON1 genotypes may not play a critical role in the modulation of endothelial vasomotor function in the intact coronary circulation. ..
  26. Edwards G, Feletou M, Weston A. Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch. 2010;459:863-79 pubmed publisher
    ..These hyperpolarise myocytes by opening various populations of myocyte potassium channels, but predominantly BK(Ca) and/or K(ATP), which are sensitive to blockade by iberiotoxin or glibenclamide, respectively. ..
  27. Momin E, Schwab K, Chaichana K, Miller Lotan R, Levy A, Tamargo R. Controlled delivery of nitric oxide inhibits leukocyte migration and prevents vasospasm in haptoglobin 2-2 mice after subarachnoid hemorrhage. Neurosurgery. 2009;65:937-45; discussion 945 pubmed publisher
    ..In addition to smooth muscle relaxation, inhibition of leukocyte migration may contribute to the therapeutic mechanism of NO. ..
  28. Williams L, Shaffer T, Greenspan J. Inhaled nitric oxide therapy in the near-term or term neonate with hypoxic respiratory failure. Neonatal Netw. 2004;23:5-13 pubmed
    ..Because iNO therapy will probably be used more frequently in nurseries over the next few years, more information on the safety and efficacy of its use in the broader neonatal population needs to be available. ..
  29. Lavi T, Karasik A, Koren Morag N, Kanety H, Feinberg M, Shechter M. The acute effect of various glycemic index dietary carbohydrates on endothelial function in nondiabetic overweight and obese subjects. J Am Coll Cardiol. 2009;53:2283-7 pubmed publisher
    ..High- compared with low-glycemic carbohydrate consumption significantly suppresses FMD in nondiabetic overweight and obese volunteers, suggesting a mechanism whereby high-glycemic meals may enhance cardiovascular risk. ..
  30. Morikawa K, Matoba T, Kubota H, Hatanaka M, Fujiki T, Takahashi S, et al. Influence of diabetes mellitus, hypercholesterolemia, and their combination on EDHF-mediated responses in mice. J Cardiovasc Pharmacol. 2005;45:485-90 pubmed
  31. Chiwororo W, Ojewole J. Dual effect of quercetin on rat isolated portal vein smooth muscle contractility. Cardiovasc J Afr. 2010;21:132-6 pubmed
    ..01) antagonised quercetin-induced relaxations, suggesting that cAMP-dependent protein kinases might have contributed, at least in part, towards the vasorelaxant effect of quercetin on rat isolated portal veins. ..
  32. Sun P, Jin X, Koyama T, Li S, Kitamura Y, Kawasaki H. R-(-)-alpha-methylhistamine, a histamine H3 receptor agonist, induces endothelium-dependent vasodilation in rat mesenteric resistance arteries. Biol Pharm Bull. 2010;33:58-63 pubmed
    ..It is also suggested that activation of histamine H(3) receptors in the endothelium releases mainly NO and partially prostaglandin I(2) and endothelium-derived hyperpolarizing factors to induce endothelium-dependent vasodilation. ..
  33. Qi S, Sun W. The effects of inhaled nitric oxide on cardiac pathology and energy metabolism in a canine model of smoke inhalation injury. Burns. 2004;30:65-71 pubmed
    ..The effects of inhaled nitric oxide (NO) on cardiac pathology and energy metabolism were studied in a canine model of smoke inhalation injury...
  34. Van Crombruggen K, Lefebvre R. Nitrergic-purinergic interactions in rat distal colon motility. Neurogastroenterol Motil. 2004;16:81-98 pubmed
    ..ATP elicits relaxations via P2Y receptors with subsequent activation of SK-channels and induces neuronal release of NO. Both nitrergic and purinergic pathways must be blocked to inhibit EFS-induced relaxations. ..
  35. Bradshaw W. The use of nitric oxide in neonatal care. Crit Care Nurs Clin North Am. 2004;16:249-55 pubmed
    ..The initial work on pulmonary vascular response in newborns who have PPHN has opened the door to seemingly endless possibilities involving many aspects of health. ..
  36. Busija D, Miller A, Katakam P, Simandle S, Erdos B. Mechanisms of vascular dysfunctionin insulin resistance. Curr Opin Investig Drugs. 2004;5:929-35 pubmed
  37. Hirata K, Yokoyama M. [Discovery and significance of NO]. Nihon Rinsho. 2004;62 Suppl 9:441-5 pubmed
  38. Adamo L, Naveiras O, Wenzel P, McKinney Freeman S, Mack P, Gracia Sancho J, et al. Biomechanical forces promote embryonic haematopoiesis. Nature. 2009;459:1131-5 pubmed publisher
    ..Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development. ..
  39. Capone C, Anrather J, Milner T, Iadecola C. Estrous cycle-dependent neurovascular dysfunction induced by angiotensin II in the mouse neocortex. Hypertension. 2009;54:302-7 pubmed publisher
  40. Lima B, Forrester M, Hess D, Stamler J. S-nitrosylation in cardiovascular signaling. Circ Res. 2010;106:633-46 pubmed publisher
    ..Here, we review the basic biochemistry of S-nitrosylation (and denitrosylation), discuss the role of S-nitrosylation in the vascular and cardiac functions of NO, and identify current and potential clinical applications. ..
  41. Osadchii L, Balueva T, Sergeev I. [Effects of the endothelial relaxing factor on the orthostatic reaction of systemic hemodynamics in rats]. Aviakosm Ekolog Med. 2003;37:27-9 pubmed
  42. Strong T, Gebska M, Champion H, Burnett A, Bivalacqua T. Stem and endothelial progenitor cells in erection biology. Int J Impot Res. 2008;20:243-54 pubmed publisher
    ..In this paper, erection physiology and stem cell biology is reviewed, and the potential application of novel cell-based therapies for the treatment of ED is discussed. ..
  43. Zheng X, Liu L, Yang D. Interaction between remnant-like lipoprotein particles and adipocytes. Int J Cardiol. 2009;133:3-7 pubmed publisher
    ..In addition, adipocytes may potentially regulate RLPs metabolism. Therefore, we hypothesized that there might be an interaction between RLPs and adipocytes. ..
  44. Gao Y, Lee R. Hydrogen peroxide is an endothelium-dependent contracting factor in rat renal artery. Br J Pharmacol. 2005;146:1061-8 pubmed
    ..Therefore, H2O2 is most likely the EDCF in rat renal artery in response to ACh stimulation. ..
  45. Mahajan A, Shabanie A, Varshney S, Marijic J, Sopher M. Inhaled nitric oxide in the preoperative evaluation of pulmonary hypertension in heart transplant candidates. J Cardiothorac Vasc Anesth. 2007;21:51-6 pubmed
    ..iNO can further improve right ventricular hemodynamics even after presumed optimization with IV vasodilators and serves as a test of PVR reversibility during the preoperative assessment of OHT candidates. ..
  46. Davison J, Homuth V, Jeyabalan A, Conrad K, Karumanchi S, Quaggin S, et al. New aspects in the pathophysiology of preeclampsia. J Am Soc Nephrol. 2004;15:2440-8 pubmed
    ..Preeclamptic women also produce novel autoantibodies that may serve to activate angiotensin receptors. These new observations raise the possibility that the treatment of preeclamptic women will soon be improved. ..
  47. Rahimian R, Chan L, Goel A, Poburko D, van Breemen C. Estrogen modulation of endothelium-derived relaxing factors by human endothelial cells. Biochem Biophys Res Commun. 2004;322:373-9 pubmed
    ..These results show that estrogen exerts a potentially important vasculo-protective effect by stimulating NO but not EDHF production. ..
  48. Yerebakan C, Ugurlucan M, Bayraktar S, Bethea B, Conte J. Effects of inhaled nitric oxide following lung transplantation. J Card Surg. 2009;24:269-74 pubmed publisher
    ..It appears to improve gas exchange and oxygenation properties. Further prospective randomized studies will aid to standardize inhalation nitric oxide therapy. ..
  49. Rakowski G, Mariak Z, Elmdhm S. [Autoregulation of the retinal circulatory system]. Klin Oczna. 2003;105:443-7 pubmed
    ..One of the most important is the endothelium derive relaxing factor (EDRF), which has been identified as endogenous nitrous oxide (NO). We have attempted to systematize current knowledge about the autoregulatory processes in the retina. ..
  50. Bell S. The story of nitric oxide: from rascally radical to miracle molecule. Neonatal Netw. 2004;23:47-51 pubmed
  51. Palm F, Onozato M, Luo Z, Wilcox C. Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. Am J Physiol Heart Circ Physiol. 2007;293:H3227-45 pubmed
  52. Kahaleh B. Vascular disease in scleroderma: mechanisms of vascular injury. Rheum Dis Clin North Am. 2008;34:57-71; vi pubmed publisher
    ..Current hypotheses in SSc vascular disease suggest a possible chemical or infectious trigger. ..
  53. Kamata K, Hosokawa M, Matsumoto T, Kobayashi T. Acetylcholine-induced vasodilation in the perfused kidney of the streptozotocin-induced diabetic rat: role of prostacyclin. J Smooth Muscle Res. 2006;42:159-70 pubmed
    ..Increased prostacyclin-signaling may occur to help compensate for the impaired endothelial function seen in the kidney in long-term diabetic states. ..