Browse > Article
http://dx.doi.org/10.5487/TR.2014.30.3.141

Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension  

Kang, Kyu-Tae (College of Pharmacy, Duksung Women's University)
Publication Information
Toxicological Research / v.30, no.3, 2014 , pp. 141-148 More about this Journal
Abstract
Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin ($PGI_2$), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions.
Keywords
Endothelium-derived relaxing factors; Small resistance arteries; Hypertension;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Forstermann, U. and Munzel, T. (2006) Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation, 113, 1708-1714.   DOI   ScienceOn
2 Gallego, M.J., Lopez Farre, A., Riesco, A., Monton, M., Grandes, S.M., Barat, A., Hernando, L., Casado, S. and Caramelo, C.A. (1993) Blockade of endothelium-dependent responses in conscious rats by cyclosporin A: effect of L-arginine. Am. J. Physiol., 264, H708-714.
3 Lee, M.Y., Jung, B.I., Chung, S.M., Bae, O.N., Lee, J.Y., Park, J.D., Yang, J.S., Lee, H. and Chung, J.H. (2003) Arsenicinduced dysfunction in relaxation of blood vessels. Environ. Health Perspect., 111, 513-517.
4 Luscher, T.F. (1994) The endothelium in hypertension: bystander, target or mediator? J. Hypertens. Suppl., 12, S105-116.   DOI
5 Taddei, S., Virdis, A., Mattei, P. and Salvetti, A. (1993) Vasodilation to acetylcholine in primary and secondary forms of human hypertension. Hypertension, 21, 929-933.   DOI   ScienceOn
6 Linder, L., Kiowski, W., Buhler, F.R. and Luscher, T.F. (1990) Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation, 81, 1762-1767.   DOI   ScienceOn
7 Treasure, C.B., Klein, J.L., Vita, J.A., Manoukian, S.V., Renwick, G.H., Selwyn, A.P., Ganz, P. and Alexander, R.W. (1993) Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation, 87, 86-93.   DOI   ScienceOn
8 Coats, P., Johnston, F., MacDonald, J., McMurray, J.J. and Hillier, C. (2001) Endothelium-derived hyperpolarizing factor: identification and mechanisms of action in human subcutaneous resistance arteries. Circulation, 103, 1702-1708.   DOI   ScienceOn
9 Ardanaz, N. and Pagano, P.J. (2006) Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Exp. Biol. Med. (Maywood), 231, 237-251.   DOI
10 Shimokawa, H. and Morikawa, K. (2005) Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in animals and humans. J. Mol. Cell. Cardiol., 39, 725-732.   DOI   ScienceOn
11 Gao, Y.J., Hirota, S., Zhang, D.W., Janssen, L.J. and Lee, R.M. (2003) Mechanisms of hydrogen-peroxide-induced biphasic response in rat mesenteric artery. Br. J. Pharmacol., 138, 1085-1092.   DOI   ScienceOn
12 Matoba, T., Shimokawa, H., Nakashima, M., Hirakawa, Y., Mukai, Y., Hirano, K., Kanaide, H. and Takeshita, A. (2000) Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J. Clin. Invest., 106, 1521-1530.   DOI   ScienceOn
13 Katusic, Z.S. (1996) Superoxide anion and endothelial regulation of arterial tone. Free Radical Biol. Med., 20, 443-448.   DOI   ScienceOn
14 Sullivan, J.C., Pollock, D.M. and Pollock, J.S. (2002) Altered nitric oxide synthase 3 distribution in mesenteric arteries of hypertensive rats. Hypertension, 39, 597-602.   DOI   ScienceOn
15 Nava, E., Llinas, M.T., Gonzalez, J.D. and Salazar, F.J. (1996) Nitric oxide synthase activity in renal cortex and medulla of normotensive and spontaneously hypertensive rats. Am. J. Hypertens., 9, 1236-1239.   DOI   ScienceOn
16 Hink, U., Li, H., Mollnau, H., Oelze, M., Matheis, E., Hartmann, M., Skatchkov, M., Thaiss, F., Stahl, R.A., Warnholtz, A., Meinertz, T., Griendling, K., Harrison, D.G., Forstermann, U. and Munzel, T. (2001) Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ. Res., 88, E14-22.   DOI   ScienceOn
17 Nithipatikom, K., Pratt, P.F. and Campbell, W.B. (2000) Determination of EETs using microbore liquid chromatography with fluorescence detection. Am. J. Physiol. Heart Circ. Physiol., 279, H857-862.   DOI
18 Kansui, Y., Fujii, K., Nakamura, K., Goto, K., Oniki, H., Abe, I., Shibata, Y. and Iida, M. (2004) Angiotensin II receptor blockade corrects altered expression of gap junctions in vascular endothelial cells from hypertensive rats. Am. J. Physiol. Heart Circ. Physiol., 287, H216-224.   DOI   ScienceOn
19 Campbell, W.B. and Harder, D.R. (1999) Endotheliumderived hyperpolarizing factors and vascular cytochrome P450 metabolites of arachidonic acid in the regulation of tone. Circ. Res., 84, 484-488.   DOI   ScienceOn
20 Fisslthaler, B., Popp, R., Kiss, L., Potente, M., Harder, D.R., Fleming, I. and Busse, R. (1999) Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature, 401, 493-497.   DOI   ScienceOn
21 Campbell, W.B., Falck, J.R. and Gauthier, K. (2001) Role of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factor in bovine coronary arteries. Med. Sci. Monit., 7, 578-584.
22 Pratt, P.F., Li, P., Hillard, C.J., Kurian, J. and Campbell, W.B. (2001) Endothelium-independent, ouabain-sensitive relaxation of bovine coronary arteries by EETs. Am. J. Physiol. Heart Circ. Physiol., 280, H1113-1121.   DOI
23 Li, P.L. and Campbell, W.B. (1997) Epoxyeicosatrienoic acids activate K+ channels in coronary smooth muscle through a guanine nucleotide binding protein. Circ. Res., 80, 877-884.   DOI   ScienceOn
24 Imig, J.D., Inscho, E.W., Deichmann, P.C., Reddy, K.M. and Falck, J.R. (1999) Afferent arteriolar vasodilation to the sulfonimide analog of 11, 12-epoxyeicosatrienoic acid involves protein kinase A. Hypertension, 33, 408-413.   DOI   ScienceOn
25 Tomioka, H., Hattori, Y., Fukao, M., Sato, A., Liu, M., Sakuma, I., Kitabatake, A. and Kanno, M. (1999) Relaxation in different-sized rat blood vessels mediated by endotheliumderived hyperpolarizing factor: importance of processes mediating precontractions. J. Vasc. Res., 36, 311-320.   DOI   ScienceOn
26 Earley, S., Heppner, T.J., Nelson, M.T. and Brayden, J.E. (2005) TRPV4 forms a novel Ca2+ signaling complex with ryanodine receptors and BKCa channels. Circ. Res., 97, 1270-1279.   DOI   ScienceOn
27 Chen, G., Suzuki, H. and Weston, A.H. (1988) Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br. J. Pharmacol., 95, 1165-1174.   DOI   ScienceOn
28 Feletou, M. and Vanhoutte, P.M. (2006) Endothelium-derived hyperpolarizing factor: where are we now? Arterioscler. Thromb. Vasc. Biol., 26, 1215-1225.   DOI   ScienceOn
29 Huang, A., Sun, D., Smith, C.J., Connetta, J.A., Shesely, E.G., Koller, A. and Kaley, G. (2000) In eNOS knockout mice skeletal muscle arteriolar dilation to acetylcholine is mediated by EDHF. Am. J. Physiol. Heart Circ. Physiol., 278, H762-768.   DOI
30 Jackson, W.F. (2000) Ion channels and vascular tone. Hypertension, 35, 173-178.   DOI
31 Vanhoutte, P.M. (2004) Endothelium-dependent hyperpolarizations: the history. Pharmacol. Res., 49, 503-508.   DOI   ScienceOn
32 Edwards, G., Dora, K.A., Gardener, M.J., Garland, C.J. and Weston, A.H. (1998) K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature, 396, 269-272.   DOI   ScienceOn
33 Edwards, G., Feletou, M., Gardener, M.J., Thollon, C., Vanhoutte, P.M. and Weston, A.H. (1999) Role of gap junctions in the responses to EDHF in rat and guinea-pig small arteries. Br. J. Pharmacol., 128, 1788-1794.   DOI   ScienceOn
34 Aszodi, A., Pfeifer, A., Ahmad, M., Glauner, M., Zhou, X.H., Ny, L., Andersson, K.E., Kehrel, B., Offermanns, S. and Fassler, R. (1999) The vasodilator-stimulated phosphoprotein (VASP) is involved in cGMP- and cAMP-mediated inhibition of agonist-induced platelet aggregation, but is dispensable for smooth muscle function. EMBO J., 18, 37-48.   DOI   ScienceOn
35 Mather, S., Dora, K.A., Sandow, S.L., Winter, P. and Garland, C.J. (2005) Rapid endothelial cell-selective loading of connexin 40 antibody blocks endothelium-derived hyperpolarizing factor dilation in rat small mesenteric arteries. Circ. Res., 97, 399-407.   DOI   ScienceOn
36 Smolenski, A., Bachmann, C., Reinhard, K., Honig-Liedl, P., Jarchau, T., Hoschuetzky, H. and Walter, U. (1998) Analysis and regulation of vasodilator-stimulated phosphoprotein serine 239 phosphorylation in vitro and in intact cells using a phosphospecific monoclonal antibody. J. Biol. Chem., 273, 20029-20035.   DOI   ScienceOn
37 Chen, L., Daum, G., Chitaley, K., Coats, S.A., Bowen-Pope, D.F., Eigenthaler, M., Thumati, N.R., Walter, U. and Clowes, A.W. (2004) Vasodilator-stimulated phosphoprotein regulates proliferation and growth inhibition by nitric oxide in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol., 24, 1403-1408.   DOI   ScienceOn
38 Fleming, I. and Busse, R. (2003) Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am. J. Physiol. Regul. Integr. Comp. Physiol., 284, R1-12.   DOI   ScienceOn
39 Kukovetz, W.R., Holzmann, S., Wurm, A. and Poch, G. (1979) Prostacyclin increases cAMP in coronary arteries. J. Cyclic Nucleotide Res., 5, 469-476.
40 Chang, J., Musser, J.H. and McGregor, H. (1987) Phospholipase A2: function and pharmacological regulation. Biochem. Pharmacol., 36, 2429-2436.   DOI   ScienceOn
41 Furchgott, R.F. and Zawadzki, J.V. (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 288, 373-376.   DOI   ScienceOn
42 Imig, J.D., Zou, A.P., Stec, D.E., Harder, D.R., Falck, J.R. and Roman, R.J. (1996) Formation and actions of 20-hydroxyeicosatetraenoic acid in rat renal arterioles. Am. J. Physiol., 270, R217-227.
43 Bunting, S., Moncada, S. and Vane, J.R. (1983) The prostacyclin--thromboxane A2 balance: pathophysiological and therapeutic implications. Br. Med. Bull., 39, 271-276.   DOI
44 Vanhoutte, P.M. (1987) Vascular physiology: the end of the quest? Nature, 327, 459-460.   DOI   ScienceOn
45 Vanhoutte, P.M. (1989) Endothelium and control of vascular function. State of the Art lecture. Hypertension, 13, 658-667.   DOI
46 Luscher, T.F. and Barton, M. (1997) Biology of the endothelium. Clin. Cardiol., 20, II-3-10.
47 Palmer, R.M., Ferrige, A.G. and Moncada, S. (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 327, 524-526.   DOI   ScienceOn
48 Reinhard, M., Halbrugge, M., Scheer, U., Wiegand, C., Jockusch, B.M. and Walter, U. (1992) The 46/50 kDa phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts. EMBO J., 11, 2063-2070.
49 Oelze, M., Mollnau, H., Hoffmann, N., Warnholtz, A., Bodenschatz, M., Smolenski, A., Walter, U., Skatchkov, M., Meinertz, T. and Munzel, T. (2000) Vasodilator-stimulated phosphoprotein serine 239 phosphorylation as a sensitive monitor of defective nitric oxide/cGMP signaling and endothelial dysfunction. Circ. Res., 87, 999-1005.   DOI   ScienceOn
50 Halbrugge, M., Friedrich, C., Eigenthaler, M., Schanzenbacher, P. and Walter, U. (1990) Stoichiometric and reversible phosphorylation of a 46-kDa protein in human platelets in response to cGMP- and cAMP-elevating vasodilators. J. Biol. Chem., 265, 3088-3093.
51 White, R.M., Rivera, C.O. and Davison, C.B. (1996) Differential contribution of endothelial function to vascular reactivity in conduit and resistance arteries from deoxycorticosteronesalt hypertensive rats. Hypertension, 27, 1245-1253.   DOI   ScienceOn
52 Bruning, T.A., Chang, P.C., Hendriks, M.G., Vermeij, P., Pfaffendorf, M. and van Zwieten, P.A. (1995) In vivo characterization of muscarinic receptor subtypes that mediate vasodilatation in patients with essential hypertension. Hypertension, 26, 70-77.   DOI   ScienceOn
53 Thybo, N.K., Mulvany, M.J., Jastrup, B., Nielsen, H. and Aalkjaer, C. (1996) Some pharmacological and elastic characteristics of isolated subcutaneous small arteries from patients with essential hypertension. J. Hypertens., 14, 993-998.
54 Furchgott, R.F. and Vanhoutte, P.M. (1989) Endotheliumderived relaxing and contracting factors. FASEB J., 3, 2007-2018.   DOI
55 Garland, C.J., Plane, F., Kemp, B.K. and Cocks, T.M. (1995) Endothelium-dependent hyperpolarization: a role in the control of vascular tone. Trends Pharmacol. Sci., 16, 23-30.   DOI   ScienceOn
56 Kang, K.T., Sullivan, J.C., Sasser, J.M., Imig, J.D. and Pollock, J.S. (2007) Novel nitric oxide synthase--dependent mechanism of vasorelaxation in small arteries from hypertensive rats. Hypertension, 49, 893-901.   DOI   ScienceOn
57 Pu, Q., Touyz, R.M. and Schiffrin, E.L. (2002) Comparison of angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP) and dual ACE/NEP inhibition on blood pressure and resistance arteries of deoxycorticosterone acetate-salt hypertensive rats. J. Hypertens., 20, 899-907.   DOI   ScienceOn
58 Li, J. and Bukoski, R.D. (1993) Endothelium-dependent relaxation of hypertensive resistance arteries is not impaired under all conditions. Circ. Res., 72, 290-296.   DOI   ScienceOn
59 Wang, D., Chabrashvili, T., Borrego, L., Aslam, S. and Umans, J.G. (2006) Angiotensin II infusion alters vascular function in mouse resistance vessels: roles of O and endothelium. J. Vasc. Res., 43, 109-119.   DOI   ScienceOn
60 Fujii, K., Tominaga, M., Ohmori, S., Kobayashi, K., Koga, T., Takata, Y. and Fujishima, M. (1992) Decreased endotheliumdependent hyperpolarization to acetylcholine in smooth muscle of the mesenteric artery of spontaneously hypertensive rats. Circ. Res., 70, 660-669.   DOI   ScienceOn
61 Deng, L.Y., Li, J.S. and Schiffrin, E.L. (1995) Endotheliumdependent relaxation of small arteries from essential hypertensive patients: mechanisms and comparison with normotensive subjects and with responses of vessels from spontaneously hypertensive rats. Clin. Sci. (Lond), 88, 611-622.   DOI
62 Rizzoni, D., Porteri, E., Castellano, M., Bettoni, G., Muiesan, M.L., Muiesan, P., Giulini, S.M. and Agabiti-Rosei, E. (1996) Vascular hypertrophy and remodeling in secondary hypertension. Hypertension, 28, 785-790.   DOI   ScienceOn
63 Cockcroft, J.R., Chowienczyk, P.J., Benjamin, N. and Ritter, J.M. (1994) Preserved endothelium-dependent vasodilatation in patients with essential hypertension. N. Engl. J. Med., 330, 1036-1040.   DOI   ScienceOn
64 Dohi, Y., Thiel, M.A., Buhler, F.R. and Luscher, T.F. (1990) Activation of endothelial L-arginine pathway in resistance arteries. Effect of age and hypertension. Hypertension, 16, 170-179.   DOI
65 Luscher, T.F., Vanhoutte, P.M. and Raij, L. (1987) Antihypertensive treatment normalizes decreased endothelium-dependent relaxations in rats with salt-induced hypertension. Hypertension, 9, III193-197.
66 Sim, M.K. and Singh, M. (1987) Decreased responsiveness of the aortae of hypertensive rats to acetylcholine, histamine and noradrenaline. Br. J. Pharmacol., 90, 147-150.   DOI   ScienceOn
67 Takase, H., Moreau, P., Kung, C.F., Nava, E. and Luscher, T.F. (1996) Antihypertensive therapy prevents endothelial dysfunction in chronic nitric oxide deficiency. Effect of verapamil and trandolapril. Hypertension, 27, 25-31.   DOI
68 Luscher, T.F., Dohi, Y. and Tschudi, M. (1992) Endotheliumdependent regulation of resistance arteries: alterations with aging and hypertension. J. Cardiovasc. Pharmacol., 19 Suppl 5, S34-42.   DOI
69 Taddei, S., Virdis, A., Mattei, P., Arzilli, F. and Salvetti, A. (1992) Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension. J. Cardiovasc. Pharmacol., 20 Suppl 12, S193-195.   DOI
70 Somers, M.J., Mavromatis, K., Galis, Z.S. and Harrison, D.G. (2000) Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone acetatesalt. Circulation, 101, 1722-1728.   DOI   ScienceOn
71 Bennett, M.A., Watt, P.A. and Thurston, H. (1993) Impaired endothelium-dependent relaxation in two-kidney, one clip Goldblatt hypertension: effect of vasoconstrictor prostanoids. J. Hypertens. Suppl., 11, S134-135.
72 Laursen, J.B., Rajagopalan, S., Galis, Z., Tarpey, M., Freeman, B.A. and Harrison, D.G. (1997) Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension. Circulation, 95, 588-593.   DOI   ScienceOn
73 Laursen, J.B., Somers, M., Kurz, S., McCann, L., Warnholtz, A., Freeman, B.A., Tarpey, M., Fukai, T. and Harrison, D.G. (2001) Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation, 103, 1282-1288.   DOI   ScienceOn
74 Dudzinski, D.M., Igarashi, J., Greif, D. and Michel, T. (2006) The regulation and pharmacology of endothelial nitric oxide synthase. Annu. Rev. Pharmacol. Toxicol., 46, 235-276.   DOI   ScienceOn
75 Virdis, A., Neves, M.F., Amiri, F., Viel, E., Touyz, R.M. and Schiffrin, E.L. (2002) Spironolactone improves angiotensininduced vascular changes and oxidative stress. Hypertension, 40, 504-510.   DOI   ScienceOn
76 Hongo, K., Nakagomi, T., Kassell, N.F., Sasaki, T., Lehman, M., Vollmer, D.G., Tsukahara, T., Ogawa, H. and Torner, J. (1988) Effects of aging and hypertension on endotheliumdependent vascular relaxation in rat carotid artery. Stroke, 19, 892-897.   DOI   ScienceOn
77 Taylor, H.J., Chaytor, A.T., Evans, W.H. and Griffith, T.M. (1998) Inhibition of the gap junctional component of endothelium-dependent relaxations in rabbit iliac artery by 18-alpha glycyrrhetinic acid. Br. J. Pharmacol., 125, 1-3.   DOI   ScienceOn