{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:14:17Z","timestamp":1761675257221},"reference-count":68,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p>Earlier we reported that dietary folate depletion causes hyperhomocysteinemia (HHcy) and arterial dysfunction in rats (Symons JD, Mullick AE, Ensunsa JL, Ma AA, and Rutledge JC. Arterioscler Thromb Vasc Biol 22: 772\u2013780, 2002). Both HHcy and low folate (LF) are risk factors for cardiovascular disease. Therefore, the dysfunction we observed could have resulted from HHcy, LF, and\/or their combination (HHcy + LF). We tested the hypothesis that HHcy-induced vascular dysfunction is more severe in the presence of LF. Four groups of rats consumed diets for \u223c10 wk that produced plasma homocysteine (\u03bcM) and liver folate (\u03bcg folate\/g liver) concentrations, respectively, of 7 \u00b1 1 and 15 \u00b1 1 (Control; Con; n = 16), 17 \u00b1 2 and 15 \u00b1 2 (HHcy; n = 17), 10 \u00b1 1 and 8 \u00b1 1 (LF; n = 14), and 21 \u00b1 2 and 8 \u00b1 1 (HHcy + LF; n = 18). We observed that maximal ACh-evoked vasorelaxation was greatest in aortas and mesenteric arteries from Con rats vs. all groups. While the extent of dysfunction was similar between LF and HHcy animals, it was less severe compared with arteries from HHcy + LF rats. Maximal ACh-evoked vasorelaxation in coronary arteries was not different between Con and LF rats, but both were greater than HHcy + LF animals. In segments of aortas, 1) ACh-evoked vasorelaxation was similar among groups after incubation with the nonenzymatic intracellular O[Formula: see text] scavenger Tiron, 2) vascular O[Formula: see text] estimated using dihydroethidium staining was greatest in HHcy + LF vs. all groups, and 3) tension development in response to nitric oxide (NO) synthase inhibition was greatest in Con vs. all other groups. We conclude that HHcy + LF evokes greater dysfunction than either HHcy alone (aortas, mesentery) or LF alone (aortas, mesentery, coronary), likely by producing more O[Formula: see text] within the vasculature and thereby reducing NO bioavailability.<\/jats:p>","DOI":"10.1152\/ajpheart.00765.2005","type":"journal-article","created":{"date-parts":[[2005,9,3]],"date-time":"2005-09-03T01:13:35Z","timestamp":1125710015000},"page":"H181-H191","source":"Crossref","is-referenced-by-count":24,"title":["Vascular dysfunction produced by hyperhomocysteinemia is more severe in the presence of low folate"],"prefix":"10.1152","volume":"290","author":[{"given":"J. David","family":"Symons","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Rutledge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Simonsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshny A.","family":"Pattathu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","unstructured":"Awad JA, Burk RF, and Roberts LJ.Effect of selenium deficiency and glutathione-modulating agents on diquat toxicity and lipid peroxidation in rats.J Pharmacol Exp Ther270: 858\u2013864, 1995."},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530130055028"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(00)00289-6"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Celermajer DS, Sorensen K, Ryalls M, Robinson J, Thomas O, Leonard OV, and Deanfield JE.Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents.J Am Coll Cardiol 22: 854\u2013858, 1993.","DOI":"10.1016\/0735-1097(93)90203-D"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.20.2479"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.00124.x"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000016248.51577.1F"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1161\/hh1101.092180"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"de Valk-de Roo GW, Stehouwer CD, Lambert J, Schalkwijk CG, van der Mooren MJ, Kluft C, and Netelenbos C.Plasma homocysteine is weakly correlated with plasma endothelin and von Willebrand factor but not with endothelium-dependent vasodilatation in healthy postmenopausal women.Clin Chem45: 1200\u20131205, 1999.","DOI":"10.1093\/clinchem\/45.8.1200"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1161\/hq0701.092000"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1177\/153537020422901109"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/27.4.592"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(88)90023-8"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(03)00174-6"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/S1047-2797(98)00027-1"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Gilfix BM, Blank DW, and Rosenblatt DS.Novel reductant for determination of total plasma homocysteine.Clin Chem42: 687\u2013688, 1997.","DOI":"10.1093\/clinchem\/43.4.687"},{"key":"R17","unstructured":"Haller J.The vitamin status and its adequacy in the elderly: an international overview.Int J Vitam Nutr Res69: 1916\u20131919, 1999."},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1042\/cs1000067"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1161\/hh0302.104724"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1046\/j.1532-5415.2002.50255.x"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.7.1832"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(97)00266-1"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10588"},{"key":"R24","unstructured":"Jones C, Vasquez-Vivary J, Briscavage J, Martasek P, Masters B, Kalyanaraman B, and Gross S.Fully-reduced pterins prevent superoxide production by eNOS: explanation for the BH4 requirement of NOSs.Acta Physiol Scand167: 645\u2013659, 1999."},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.11.1161"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.3.H981"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1007\/BF00965847"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.2.422"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.13.6.771"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.3.H970"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00392-5"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118771"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(90)86141-H"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/58.4.M354"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2002.01059.x"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1974.tb03714.x"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199707243370403"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2002.6467"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-004-0219-5"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.1.248"},{"key":"R41","doi-asserted-by":"crossref","unstructured":"Simonsen U, Wadsworth RM, Buus NH, and Mulvany MJ.In vitro simultaneous measurements of relaxation and nitric oxide concentration in rat superior mesenteric artery.J Physiol516: 271\u2013282, 2002.","DOI":"10.1111\/j.1469-7793.1999.271aa.x"},{"key":"R42","unstructured":"Spijkerman AMW, Smulders YM, Kostense PJ, Henry RMA, Becker A, Teerlink T, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, and Stehouwer CDA.S-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study.Arterioscler Thromb Vasc Biol25: 778\u2013784, 2004."},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200208000-00020"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200307000-00002"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.11.1129"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.4.H1575"},{"key":"R47","unstructured":"Symons JDand Simonsen U.Hyperhomocysteinemia limits coronary arteriolar nitric oxide production (Abstract).FASEB J18: A200.7, 2004."},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01168.2002"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000014588.71807.0A"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.2.433"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.87.2.574"},{"key":"R52","unstructured":"Tamura T.Microbiological assay of folates.Folic Acid Metabolism in Health and Disease.New York: Wiley-Liss, 1990, p. 121\u2013188."},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00361.2003"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00809-3"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64166-1"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.27.17012"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.4.335"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.3.237"},{"key":"R59","doi-asserted-by":"crossref","unstructured":"Verhoef P, Kok F, and Kruyssen D.Plasma total homocysteine, B vitamins, and risk of coronary atherosclerosis.Arterioscler Thromb Vasc Biol17: 435\u2013441, 1997.","DOI":"10.1161\/01.ATV.17.5.989"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.1.185"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.7.2282"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.8.2542"},{"key":"R63","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100747200"},{"key":"R64","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.4.F671"},{"key":"R65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501719102"},{"key":"R66","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(03)00142-4"},{"key":"R67","doi-asserted-by":"publisher","DOI":"10.1161\/hq0901.096582"},{"key":"R68","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000112581.96154.EA"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00765.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T23:45:42Z","timestamp":1626479142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00765.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":68,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1152\/ajpheart.00765.2005"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00765.2005","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1]]}}}