Abstract
In hypertension, endothelium-dependent relaxation is attenuated and this attenuation contributes to the increased peripheral resistance. However, the role of endothelium-derived hyperpolarizing factor (EDHF) in the arteries of hypertensive rats remains unclear. Therefore, the aim of this study was to evaluate the role of EDHF in the femoral resistance arteries of hypertensive rats. The femoral resistance arteries were isolated from 5-, 15- and 25-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Changes in internal diameter were examined with videomicroscopy. EDHF-mediated dilatation was determined by differences between the degree of acetylcholine (ACh)-induced dilatation in the presence of NG-monomethy-L-arginine (L-NMMA) plus a prostaglandin I2 inhibitor (indomethacin) and the degree of such dilatation in the presence of L-NMMA, indomethacin and KCl. Charybdotoxin (CTx) and apamin (a Ca2+-activated K+ channel [KCa] inhibitor)−sensitive EDHF dilatation was also compared between in 5-, 15- and 25-week-old SHR and WKY. ACh-induced vasodilatation was not different between 5-week-old SHR and WKY. There was no difference between NO- and EDHF-mediated vasodilatation in 5-week-old rats. ACh-induced vasodilatation was weaker in 15-week-old SHR than in WKY. NO-mediated vasodilatation did not differ between the two groups. EDHF-mediated dilatation was attenuated in SHR but not in WKY. ACh-induced dilatation was weaker in 25-week-old SHR than in WKY. NO- and EDHF-mediated vasodilatation were attenuated in SHR but not WKY. EDHF-mediated vasodilatation was attenuated before the loss of NO-mediated vasodilatation in the femoral resistance arteries of SHR. The attenuation of this vasodilatation was mediated by the CTx plus apamin–sensitive EDHF.
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Bassenge E : Control of coronary blood flow by autacoids. Basic Res Cardiol 1995; 90: 125–141.
Brandes RP, Schmitz-Winnenthal FH, Feletou M, et al: An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice. Proc Natl Acad Sci U S A 2000; 97: 9747–9752.
Panza JA, Quyyumi AA, Brush JE, Epstein SE : Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990; 323: 22–27.
Luscher TF : The endothelium in hypertension: bystander, target or mediator? J Hypertens Suppl 1994; 12: S105–S116.
Rajagopalan S, Kurz S, Munzel T, et al: Angiotensin II–mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. J Clin Invest 1996; 97: 1916–1923.
Kojda G, Harrison DG : Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovasc Res 1999; 43: 562–571.
Sofola OA, Knill A, Hainsworth R, Drinkhill M : Changes in endothelial function in mesenteric arteries of Sprague-Dawley rats fed a high salt diet. J Physiol 2002; 543: 255–260.
Bussemaker E, Popp R, Fisslthaler B, Larson CM, Fleming I : Aged spontaneously hypertensive rats exhibit a selective loss of EDHF-mediated relaxation in the renal artery. Hypertension 2003; 42: 562–568.
Fujii K, Tominaga M, Ohmori S, et al: Decreased endothelium-dependent hyperpolarization to acetylcholine in smooth muscle of the mesenteric artery of spontaneously hypertensive rats. Circ Res 1992; 70: 660–669.
Goto K, Fujii K, Kansui Y, Iida M : Changes in endothelium-derived hyperpolarizing factor in hypertension and ageing: response to chronic treatment with renin-angiotensin system inhibitors. Clin Exp Pharmacol Physiol 2004; 31: 650–655.
Hecker M, Bara AT, Bauersachs J, Busse R : Characterization of endothelium-derived hyperpolarizing factor as a cytochrome P450−derived arachidonic acid metabolite in mammals. J Physiol 1994; 481: 407–414.
Bauersachs J, Hecker M, Busse R : Display of the characteristics of endothelium-derived hyperpolarizing factor by cytochrome P450−derived arachidonic acid metabolite in the coronary microcirculation. Br J Pharmacol 1994; 113: 1548–1553.
Edwards G, Dora KA, Gardener MJ, Garland CJ, Weston AH : K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature 1998; 396: 269–272.
Taylor HJ, Chaytor AT, Evans WH, Griffith TM : Inhibition of the gap junctional component of endothelium-dependent relaxations in rabbit iliac artery by 18α-glycyrrhetinic acid. Br J Pharmacol 1998; 125: 1–3.
Matoba T, Shimokawa H, Nakashima M, et al: Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest 2000; 106: 1521–1530.
Matoba T, Shimokawa H, Kubota H, et al: Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in human mesenteric arteries. Biochem Biophys Res Commun 2002; 290: 909–913.
Zygmunt PM, Ryman T, Hogestatt ED : Regional differences in endothelium-dependent relaxation in the rat: contribution of nitric oxide and nitric oxide–independent mechanisms. Acta Physiol Scand 1995; 155: 257–266.
Wigg SJ, Tare M, Tonta MA, O'Brien RC, Meridith IT, Parkington HC : Comparison of the effects of diabetes mellitus on an EDHF-dependent and an EDHF-independent artery. Am J Physiol 2001; 281: H232–H240.
Parkington HC, Chow JAM, Evans RG, Coleman HA, Tare M : Role for endothelium-derived hyperpolarizing factor in vascular tone in rat mesenteric and hindlimb circulation in vivo. J Physiol 2002; 542: 929–937.
Shimizu E, Ohyanagi M, Masutani M, Iwasaki T : A decrease in the amount and function of stimuratory GTP-binding protein in the resistance small artery from spontaneously hypertensive rats. Hypertens Res 2002; 25; 743–749.
Urakami-Harasawa L, Shimokawa H, Nakashima M, Egashira K, Takeshita A : Importance of endothelium-derived hyperpolarizing factor in human arteries. J Clin Invest 1997; 100: 2793–2799.
Doughty JM, Plane F, Langton PD : Charybdotoxin and apamin block EDHF in rat mesenteric artery if selectively applied to the endothelium. Am J Physiol 1999; 276: H1107–H1112.
Ma YH, Gebremedhin D, Schwartzman ML, et al: 20-Hydroxyeicosatetraenoic acid is an endogenous vasoconstrictor of canine renal arcuate arteries. Circ Res 1993; 72: 126–136.
Harder DR, Gebremedhin D, Narayanan J, et al: Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. Am J Physiol 1994; 266: H2098–H2107.
Sandow SL, Bramich NJ, Bandi HP, Rummery NM, Hill CE : Structure, function,, and endothelium-derived hyperpolarizing factor in the caudal artery of the SHR and WKY rat. Arterioscler Thromb Vasc Biol 2003; 23: 822–828.
Ueda A, Ohyanagi M, Koida S, Iwasaki T : Enhanced release of endothelium-derived hyperpolarizing factor in small coronary arteries from rats with congestive heart failure. Clin Exp Pharmacol Physiol 2005; 32: 615–621.
Chang HR, Lee RP, Wu CY, Chen HI : Nitric oxide in mesenteric vascular reactivity: a comparison between rats with normotension and hypertension. Clin Exp Pharmacol Physiol 2002; 29: 275–280.
Shimokawa H, Yasutake H, Fujii K, et al: The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol 1996; 28: 703–711.
Kaw S, Hecker M : Endothelium-derived hyperpolarizing factor, but not nitric oxide or prostacyclin release, is resistant to menadione-induced oxidative stress in the bovine coronary artery. Naunyn Schmiedebergs Arch Pharmacol 1999; 359: 133–139.
Nishikawa Y, Steep DW, Chilian WM : In vivo location and mechanism of EDHF-mediated vasodilatation in canine coronary microcirculation. Am J Physiol 1999; 277: H1252–H1259.
Eckman DM, Hopkins N, McBride C, Keef KD : Endothelium-dependent relaxation and hyperpolarization in guinea-pig coronary artery: role of epoxyeicosatrienoic acid. Br J Pharmacol 1998; 124: 181–189.
Coleman HA, Tare M, Parkington HC, Arkington HC : K+ currents underlying the action of endothelium-derived hyperpolarizing factor in guinea-pig, rat and human blood vessels. J Physiol 2001; 531: 359–373.
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Mori, Y., Ohyanagi, M., Koida, S. et al. Effects of Endothelium-Derived Hyperpolarizing Factor and Nitric Oxide on Endothelial Function in Femoral Resistance Arteries of Spontaneously Hypertensive Rats. Hypertens Res 29, 187–195 (2006). https://doi.org/10.1291/hypres.29.187
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DOI: https://doi.org/10.1291/hypres.29.187