Endothelium-dependent relaxation

Three years later Robert F Furchgott discov ered that the relaxing of smooth muscles such as blood vessel walls was stimulated by an unknown substance produced in the lining of the blood vessels (the endothelium) He called this substance the endothelium-dependent relaxing factor or EDRF and in 1986 showed that EDRF was NO Louis J Ignarro reached the same conclusion at about the same time Further support was provided by Salvador Moncada who showed that endothelial cells did in deed produce NO and that the l arginine to l citrulline conversion was responsible... 

Andrews, Fi.E., Bruckdorfer, K.R., Dunn, R.C. and Jacobs, M. (1987). Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta. Nature (Lond.) 327, 237-239. 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

Superoxide dismutase recovers altered endothelium-dependent relaxation in diabetic rat aorta. Am. J. Physiol. 261, H1086-H1094. 

Kamata, K., Miyata, N. and Kasuya, Y. (1989). Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozocin-induced diabetic rats. Br. J. Pharmacol. 97, 614-618. 

Oyama, Y., Kawasaki, H., Flattori, Y. and Kanno, M. (1986). Attenuation of endothelium-dependent relaxation in aorta from diabetic rats. Eur. J. Pharmacol. 131, 75-78. 

P2Y receptors that are found on endothelial cells elicit a Ca2+-dependent release of endothelium-dependent relaxing factor (EDRF) and vasodilation. A secondary activation of a Ca2+-sensitive phospholipase A2 increases the synthesis of endothelial prostacyclin, which limits the extent of intravascular platelet aggregation following vascular damage and platelet stimulation. The P2Y-mediated vasodilation opposes a vasoconstriction evoked by P2X receptors located on vascular smooth muscle cells. The latter elicit an endothelial-independent excitation (i.e. constriction). P2Y receptors are also found on adrenal chromaffin cells and platelets, where they modulate catecholamine release and aggregation respectively. 

Rapoport RM, Draznin MB, Murad F (1983) Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation. Nature 306 174-176... 

Raeymaekers The data indicate that it is SERCA3 that fills the stores that are involved in the endothelium-dependent relaxation. At face value, the separate data indicate that this store could be connected to TRPC4. 

While several studies reported that PLB was present in smooth muscle, very little was known about its role in Ca2+ handling. Some evidence suggested that in addition to A-kinase pathway phosphorylation, activation of the G -kinase pathway was associated with PLB phosphorylation. The latter was of particular interest to vascular smooth muscle, for which endothelium-dependent relaxation via nitric oxide (NO) made the mechanism of G-kinase-mediated relaxation of considerable physiological significance (Karczewski et al 1998). 

Liu LH, Paul RJ, Sutliff RL et al 1997 Defective endothelium-dependent relaxation of vascular smooth muscle and endothelial cell Ca2+ signaling in mice lacking sarco(endo)plasmic reticulum Ca2+-ATPase isoform 3. J Biol Chem 272 30538—30545... 

Kang, S. Y., Kim, S. H., Schini-Kerth, V. B., and Kim, N. D. (1995a). Dietary ginsenosides improve endothelium-dependent relaxation in the thoratic aorta of hypercholesterolemic rabbit. Gen. Pharmacol. 26, 483—487. 

Moroi M, Akatsuka N, Eukazawa M, Hara K, Ishikawa M, Aikawa J, Namiki A, Yamaguchi T. (1994) Endothelium-dependent relaxation by angiotensinconverting enzyme inhibitors in canine femoral arteries. Am J Physiol 266 H583-H589. 

Karim, M., McCormick, K., and Kappagoda, C.T., Effect of cocoa extracts on endothelium-dependent relaxation, J. Nutr., 130, 2105S, 2000. 

Buckley, C, Bund SJ, McTaggart F et al. Oxidized low-density lipoproteins inhibit endothelium-dependent relaxations in isolated large and small rabbit coronary arteries. J. Auton. Pharmacol. 16,... 

Acetylcholine dilates all blood vessels causing flushing and fall in blood pressure. The vasodilatation is mediated through the release of endothelium dependent relaxing factor (EDRF). The fall in blood pressure is because of decrease in total peripheral resistance and cardiac output in anaesthetized animals. 

Fukuto, J. M., Wood, K. S., Byrns, R. E., and Ignarro, L. J. (1990). N -Amino-L-arginine A new potent antagonist of L-arginine-mediated endothelium-dependent relaxation. Biochem. Biophys. Res. Commun. 168, 458-465. 

Palmer, R. M. J., Rees, D. D., Ashton, D. S., and Moncada, S. (1988b). L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem. Biophys. Res. Commun. 153, 1251-1256. 

Singer, H. A., and Peach, M. J. (1983). Endothelium-dependent relaxation of rabbit aorta. 

Rose Meyer RB, Hope W (1990) Evidence that A2 purinoceptors are involved in endothelium-dependent relaxation of the rat thoracic aorta. Br J Pharmacol 100(3) 576-580 Rubio R, Ceballos G (2003) Sole activation of three luminal adenosine receptor subtypes in different parts of coronary vasculature. Am J Physiol 284(1) H204-H214 Safran N, Shneyvays V, Balas N, Jacobson KA, Nawrath H, Shainberg A (2001) Cardioprotective effects of adenosine A3 and A3 receptor activation during hypoxia in isolated rat cardiac myocytes. Mol Cell Biochem 217(1-2) 143-152 Salvatore CA, Tilley SL, Latour AM, Fletcher DS, Roller BH, Jacobson MA (2000) Disruption of the A3 adenosine receptor gene in mice and its effect on stimulated inflammatory cells. J Biol Chem 275(6) 4429-4434... 

Djuric, DM., Andjelkovic, IZ, 1995. The evidence for histamine H3 receptor-mediated endothelium-dependent relaxation in isolated rat aorta. Mediators Inflammation 4, 217-221. 

Djuric, D.M., Nesic, M.T., Andjelkovic, I.Z., 1996. Endothelium-dependent relaxation of rat aorta to a histamine H3 agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na+, K+-ATPase. Mediators Inflammation 5, 69-74. 

Aldini G, Carini M, Piccoli A, Rossoni G Facino RM. 2003. Procyanidins from grape seeds protect endothelial cells from peroxynitrite damage and enhance endothelium-dependent relaxation in human artery New evidences for cardio-protection. Life Sci 73 2883-2898. 

Knock GA, Mahn K, Mann GE, Ward JP, Aaronson PI. 2006. Dietary soy modulates endothelium-dependent relaxation in aged male rats Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity. Free Radic Biol Med 41 731-739. 

Mishra SK, Abbot SE, Choudhury Z, Cheng M, Khatab N, Maycock NJ, Zavery A, Aaronson PI. 2000. Endothelium-dependent relaxation of rat aorta and main pulmonary artery by the phytoestrogens genistein and daidzein. Cardiovasc Res 46 539-546. 

T Murohara, K Kugiyama, M Ohgushi, S Sugiyama, Y Ohta, H Yasue. LPC in oxidized LDL elicits vasocontraction and inhibits endothelium-dependent relaxation. Am J Physiol 267 H2441-H2449, 1994. 

Sellke FW, Wang SY Friedman M, et al. Basic FGF enhances endothelium-dependent relaxation of the collateral-perfused coronary microcirculation. Am J Physiol I 994 267(4 Pt 2) H1303-H13 I I. 

Recent findings [117] suggest that native LDL and Ox-LDL directly inactivate EDRF but do not attenuate formation of EDRF in cultured and native endothelial cells after short-term exposure. A direct inactivation of EDRF by the lipoproteins rather than an effect on the target-organ smooth muscle has been involved [117]. It has been reported that contractions to native LDL are due to its oxidation in the organ chamber, and that Ox-LDL, but not native LDL, inhibits endothelium-dependent relaxations to 5HT. In fact, the native-LDL molecule is known to be unstable after its isolation from the blood, is readily auto-oxidised in the presence of air, and is highly sensitive to metal-catalyzed oxidation [118],... 

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