Endothelium-derived hyperpolarizing factor

Campbell, W. B., Gebremedhin, D., Pratt, P. F., and Harder, D. R. 1996. Identification of epoxye-icosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ. Res. 78 415 123. 

Edwards, G., Gardener, M. J., Feletou, M., Brady, G., Vanhoutte, P. M., and Weston, A. H. 1999. Further investigation of endothelium-derived hyperpolarizing factor (EDHF) in rat hepatic artery studies using 1-EBIO and ouabain. Br. J. Pharmacol. 128 1064-1070. 

Si, H., Heyken, W. T., Wolfle, S. E., Tysiac, M., Schubert, R., Grgic, I., Vilianovich, L.,Giebing, G., Maier, T., Gross, V., Bader, M., de, W. C., Hoyer, J., and Kohler, R. 2006. Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel. Circ. Res. 99 537-544. 

Flow-dependent changes in vessel diameter contribute to the optimization of circulatory function and are mediated via shear stress-induced release of NO, vasodilator prostanoids, and a putative endothelium-derived hyperpolarization factor or EDHF (Griffith, 2002). There is growing evidence that NO/prostanoid-independent relaxations involve direct hetero-cellular signaling between endothelium and smooth muscle cells via gap junctions. 

Nitric oxide, endothelium-derived hyperpolarizing factor and prostaglandins Renal and cardiac fibrosis Glomerular function in the IPRK Disadvantages of the IPRK model Advantages of the IPRK model... 

Nitric oxide, endothelium-derived hyperpolarizing factor and prostaglandins... 

The IPRK was used to demonstrate that excess nitric oxide (NO) and possibly endothelium-derived hyperpolarizing factor (EDHF), contribute to impaired autoregulation after ischemic injury as described above [328]. A role for EDHF in renal vascular resistance and in glomerular and tubular function was first observed in the IPRK by Bhardwaj and Moore [386] and by Rademacher et al [387-8]. Others observed that manipulating NO can alter medullary oxygenation in the IPRK [288]. An increased endothelium-dependent vasodilator response to acetylcholine was observed in IPRK from cirrhotic rats [390]. Portal vein ligation also... 

EDHF endothelium-derived hyperpolarizing factor H E hematoxylin and eosin... 

The interest in the vasodilator action of endocannahinoids was further stimulated by a report in 1996 that the mesenteric vasodilation attributable to an endothelium-derived hyperpolarizing factor (EDHF) is sensitive to inhibition by SR141716 (Randall et al. 1996). The corollary of this finding was that EDHF might be an endocannabinoid released from the vascular endothelium and acting at... 

Fleming I, Schermer B, Popp R, Busse R (1999) Inhibition ofthe production of endothelium-derived hyperpolarizing factor by cannabinoid receptor agonists. Br J Pharmacol 126 949-960... 

Randall MD, Kendall DA (1997) Involvement of a cannabinoid in endothelium-derived hyperpolarizing factor-mediated coronary vasorelaxation. Eur J Pharmacol 335 205-209... 

Randall MD, Kendall DA (1998) Anandamide and endothelium-derived hyperpolarizing factor act via a common vasorelaxant mechanism in rat mesentery. Eur J Pharmacol 346 51-53... 

Various EETs have been measured in tissues as well as physiological fluids such as urine (G. FitzGerald, 1990). Biologically active lipids, originally defined as an endothelium-derived hyperpolarizing factor and an inhibitor of Na /K ATPase found in the thick ascending loop of Henley cells, were structurally characterized as 1 (/ ), 2(5)-EET and 20-HETE, both derived from cytochrome P-450-mediated metabolism of AA [35]. Interestingly, the EETs can readily form CoA esters and participate in reacylation of... 

Campbell, W.B. and D.R. Harder (1999). Endothelium-derived hyperpolarizing factors and vascular cytochrome P450 metabolites of arachi-donic acid in the regulation of tone. Circ. Res. 84, 484-488, and cited references. 

A number of factors, including tissue damage, allergic reactions, viral infections, and other inflammatory events, activate a series of proteolytic reactions that generate bradykinin and kallidin in tissues. These peptides contribute to inflammatory responses as autacoids that act locally to produce pain, vasodilation, and increased vascular permeability. Much of their activity is due to stimulation of the release of potent mediators such as prostaglandins, NO, or endothelium-derived hyperpolarizing factor (EDHF). 

Cyclic adenosine monophosphate Endothelium-derived hyperpolarizing factors Cyclic guanosine monophosphate Heart failure... 

Kagota, S., Yamaguchi, Y., Nakamura, K., Sugiura, T., Waku, K., and Kunitomo, M. (2001) 2-Arachidonoyl-glycerol, a candidate of endothelium-derived hyperpolarizing factor, European Journal of Pharmacology 415 233-238. 

Randall, M.D., McCulloch, A. I., and Kendall, D.A. (1997). Comparative pharmacology of endothelium-derived hyperpolarizing factor and anandamide in rat isolated mesentery. European Journal of Pharmacology, 333 191-197. 

Besides FAME and SAME, other fatty acids have also been shown to have vasoactive properties. For example, AA is a 20-carbon polyunsaturated (d-6 fatty acid (20 4 n-6), which is an essential fatty acid found in peanut oil and eggs/meats. AA has been shown to cause endothelium- and iC-independent vasodilation [13] metabolized by cytochrome P450 enzymes in the liver to form epoxyeicosatrienoic acid (EET) (Figure 2). EETs are produced in the vascular endothelium and causes potent vasodilation in renal, mesenteric, coronary, and cerebral arterioles in a variety of mammalian species [14-17]. EETs hyperpolarize VSMCs by activating calcium-activated potassium chaimels (Kca) chaimels. Several investigators have proposed that EET may serve as a possible candidate for endothelium-derived hyperpolarizing factor (The exact structure and identity of EDHF is currently unknown) due to the fact that EETs are produced in the endothelium [18]. EETs can lower systemic blood pressure in SHR-hypertensive rats suggesting possible therapeutic validity [19, 20]. 

The regulation of the vascular tone by the endothelium is due predominantly to the endothelial formation of several potent vasorelaxing factors involving nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin (PGI2) (Fig. 76.1). 

Dal-Ros S, Bronner C, Schott C, Kane MO, Chataigneau M, Schini-Kerth VB, Chataigneau T (2009) Angiotensin U-induced h5 rtension is associated with a selective inhibition of endothelium-derived hyperpolarizing factor-mediated responses in the rat mesenteric artery. J Pharmacol Exp Ther 328(2) 478 86. doi 10.1124/jpet.l08.145326 Rakici O, Kiziltepe U, Coskun B, Aslamaci S, Akar F (2005) Effects of resveratrol on vascular tone and endothelial function of human saphenous vein and internal mammary artery. Int J Cardiol 105(2) 209-215... 

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