The FASEB Journal, Vol 3, 2007-2018, Copyright © 1989 by The Federation of American Societies for Experimental Biology

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Endothelium-derived relaxing and contracting factors

RF Furchgott and PM Vanhoutte
Department of Pharmacology, State University of New York, Brooklyn 11203.

Endothelium-dependent relaxation of blood vessels is produced by a large number of agents (e.g., acetylcholine, ATP and ADP, substance P, bradykinin, histamine, thrombin, serotonin). With some agents, relaxation may be limited to certain species and/or blood vessels. Relaxation results from release of a very labile non-prostanoid endothelium-derived relaxing factor (EDRF) or factors. EDRF stimulates guanylate cyclase of the vascular smooth muscle, with the resulting increase in cyclic GMP activating relaxation. EDRF is rapidly inactivated by hemoglobin and superoxide. There is strong evidence that EDRF from many blood vessels and from cultured endothelial cells is nitric oxide (NO) and that its precursor is L-arginine. There is evidence for other relaxing factors, including an endothelium-derived hyperpolarizing factor in some vessels. Flow-induced shear stress also stimulates EDRF release. Endothelium-dependent relaxation occurs in resistance vessels as well as in larger arteries, and is generally more pronounced in arteries than veins. EDRF also inhibits platelet aggregation and adhesion to the blood vessel wall. Endothelium-derived contracting factors appear to be responsible for endothelium-dependent contractions produced by arachidonic acid and hypoxia in isolated systemic vessels and by certain agents and by rapid stretch in isolated cerebral vessels. In all such experiments, the endothelium-derived contracting factor appears to be some product or by-product of cyclooxygenase activity. Recently, endothelial cells in culture have been found to synthesize a peptide, endothelin, which is an extremely potent vasoconstrictor. The possible physiological roles and pathophysiological significance of endothelium-derived relaxing and contracting factors are briefly discussed.

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				M. Pretorius, D. A. Rosenbaum, J. Lefebvre, D. E. Vaughan, and N. J. Brown Smoking Impairs Bradykinin-Stimulated t-PA Release Hypertension, March 1, 2002; 39(3): 767 - 771. [Abstract] [Full Text] [PDF]

				C. Ibarra-Alvarado, J. Galle, V. O. Melichar, A. Mameghani, and H. H. H. W. Schmidt Phosphorylation of Blood Vessel Vasodilator-Stimulated Phosphoprotein at Serine 239 as a Functional Biochemical Marker of Endothelial Nitric Oxide/Cyclic GMP Signaling Mol. Pharmacol., February 1, 2002; 61(2): 312 - 319. [Abstract] [Full Text] [PDF]

				P.M. Vanhoutte Ageing and endothelial dysfunction Eur. Heart J. Suppl., February 1, 2002; 4(suppl_A): A8 - A17. [Abstract] [PDF]

				C.Y. Yu, N.M. Boyd, S.J. Cringle, E.N. Su, V.A. Alder, and D.Y. Yu Acetylcholine-induced Vasodilation of Isolated Pulpal Arterioles Journal of Dental Research, November 1, 2001; 80(11): 1995 - 1999. [Abstract] [PDF]

				T. Lauer, M. Preik, T. Rassaf, B. E. Strauer, A. Deussen, M. Feelisch, and M. Kelm Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action PNAS, October 12, 2001; (2001) 221381098. [Abstract] [Full Text] [PDF]

				D. Z. Ellis, J. A. Nathanson, J. Rabe, and K. J. Sweadner Carbachol and Nitric Oxide Inhibition of Na,K-ATPase Activity in Bovine Ciliary Processes Invest. Ophthalmol. Vis. Sci., October 1, 2001; 42(11): 2625 - 2631. [Abstract] [Full Text] [PDF]

				G.-W. He and Z.-G. Liu Comparison of Nitric Oxide Release and Endothelium-Derived Hyperpolarizing Factor-Mediated Hyperpolarization Between Human Radial and Internal Mammary Arteries Circulation, September 18, 2001; 104 (2009): I-344 - I-349. [Abstract] [Full Text] [PDF]

				E. Ihara, D. N Derkach, K. Hirano, J. Nishimura, H. Nawata, and H. Kanaide Ca2+ influx in the endothelial cells is required for the bradykinin-induced endothelium-dependent contraction in the porcine interlobar renal artery J. Physiol., August 1, 2001; 534(3): 701 - 711. [Abstract] [Full Text] [PDF]

				J. P. J. Halcox, S. Narayanan, L. Cramer-Joyce, R. Mincemoyer, and A. A. Quyyumi Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2470 - H2477. [Abstract] [Full Text] [PDF]

				N. Harada, S. Sakamoto, Y. Niwa, and Y. Nakaya Involvement of adenosine in vascular contractile preconditioning Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2911 - H2919. [Abstract] [Full Text] [PDF]

				X. Zhang and T. H. Hintze cAMP Signal Transduction Cascade, a Novel Pathway for the Regulation of Endothelial Nitric Oxide Production in Coronary Blood Vessels Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 797 - 803. [Abstract] [Full Text] [PDF]

				S. Cuzzocrea, D. P. Riley, A. P. Caputi, and D. Salvemini Antioxidant Therapy: A New Pharmacological Approach in Shock, Inflammation, and Ischemia/Reperfusion Injury Pharmacol. Rev., March 1, 2001; 53(1): 135 - 159. [Abstract] [Full Text] [PDF]