{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:31:39Z","timestamp":1790854299761,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:p>Endothelium\u2010dependent vasodilatation declines with advancing age in humans independently of disease. The mechanisms responsible for this decline are not clear. We determined whether the age\u2010related reduction in endothelium\u2010dependent vasodilatation in response to acetylcholine reflects a specific agonist\u2010related defect or rather a more general endothelial cell vasomotor abnormality. Twenty\u2010two young (23\u201035 years) and 41 older (50\u201076 years) healthy men were studied. Forearm blood flow (FBF) responses to intra\u2010arterial infusions of acetylcholine, bradykinin, substance P, isoproterenol (isoprenaline) and sodium nitroprusside were measured by strain\u2010gauge plethysmography. There were no differences in resting FBF between the young (3.9 \u00b1 0.2 ml (100 ml tissue)<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>) and older men (4.0 \u00b1 0.2 ml (100 ml tissue)<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>). The increase in FBF at the highest dose of acetylcholine was \u223c30 % lower (<jats:styled-content><jats:italic>P<\/jats:italic> &lt; 0.01<\/jats:styled-content>) in the older (from 4.0 \u00b1 0.2 to 12.3 \u00b1 0.7 ml (100 ml tissue)<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>) compared with young men (from 3.9 \u00b1 0.2 to 17.1 \u00b1 1.5 ml (100 ml tissue)<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>). In contrast to acetylcholine, the FBF responses to the other endothelial agonists were not impaired with age. The maximum increases in FBF in response to bradykinin (19.2 \u00b1 1.0 <jats:italic>vs<\/jats:italic>. 20.2 \u00b1 0.9 ml (100 ml tissue)<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>), substance P (15.1 \u00b1 0.8 <jats:italic>vs<\/jats:italic>. 16.8 \u00b1 0.7 ml (100 ml tissue)<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>) and isoproterenol (17.5 \u00b1 0.9 <jats:italic>vs<\/jats:italic>. 17.5 \u00b1 0.9 ml (100 ml tissue)<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>) were not significantly different between the older and young subjects. There were no age\u2010related differences in the FBF responses to sodium nitroprusside. These results demonstrate that, although acetylcholine\u2010induced vasodilatation is impaired with age, forearm endothelial vasodilatation in reponse to bradykinin, substance P and isoproterenol are well preserved in healthy men. Moreover, these findings suggest that agonist\u2010stimulated endothelium\u2010dependent vasodilatation is not universally impaired with age.<\/jats:p>","DOI":"10.1113\/jphysiol.2002.019166","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:15:15Z","timestamp":1027898115000},"page":"255-262","source":"Crossref","is-referenced-by-count":67,"title":["Evidence for agonist\u2010specific endothelial vasodilator dysfunction with ageing in healthy humans"],"prefix":"10.1113","volume":"542","author":[{"given":"Christopher A.","family":"DeSouza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Clevenger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared J.","family":"Greiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek T.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta L.","family":"Hoetzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda F.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Stauffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,7]]},"reference":[{"key":"e_1_2_5_2_1","volume-title":"Americn Heart Association","author":"American Heart Association","year":"2001"},{"issue":"7","key":"e_1_2_5_3_1","first-page":"S179","article-title":"Interpretation of the acetylcholine test of endothelial cell dysfunction in hypertension","volume":"10","author":"Angus J. A.","year":"1992","journal-title":"Journal of Hypertension"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017630"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.2.2.130"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1113"},{"key":"e_1_2_5_7_1","first-page":"155","volume-title":"Goodman & Gillman's The Pharmacological Basis of Therapeutics","author":"Brown J. H.","year":"2001"},{"key":"e_1_2_5_8_1","first-page":"645","volume-title":"Goodman & Gillman's The Pharmacological Basis of Therapeutics","author":"Brown N. J.","year":"2001"},{"key":"e_1_2_5_9_1","first-page":"V18","article-title":"Mechanisms of nitric oxide release from the vascular endothelium","volume":"87","author":"Busse R.","year":"1993","journal-title":"Circulation"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022403308819"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.30.4.918"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.9.851"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80524-4"},{"key":"e_1_2_5_14_1","first-page":"87","article-title":"Blood chollinesterase levels in the elderly and new born","volume":"17","author":"Chan L.","year":"1995","journal-title":"Malaysian Journal of Pathology"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.6.2106"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1994.tb04358.x"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.9.2293"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.18.3.362"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.12.1351"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.88.1.77"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0660697"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.4.849"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.90.1.35"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199204002-00063"},{"key":"e_1_2_5_25_1","first-page":"13","volume-title":"Atherosclerosis and Coronary Artery Disease","author":"Kannel W. B.","year":"1996"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700928"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1988.196"},{"key":"e_1_2_5_28_1","volume-title":"Anthropometric Standardization Reference Manual","author":"Lohman T. G.","year":"1988"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0920133"},{"key":"e_1_2_5_30_1","first-page":"802","article-title":"Decline in beta adrenergic receptor\u2010mediated vascular relaxation with aging in man","volume":"2393","author":"Pan H. Y. M.","year":"1986","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90664-5"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.6.1732"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.1.104"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1991.tb33155.x"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0841"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.29.1.274"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.38.2.274"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.29.3.736"},{"key":"e_1_2_5_39_1","first-page":"1981","article-title":"Aging and endothelial function in normotensive subjects and patients with essential hypertension","volume":"91","author":"Taddei S.","year":"1995","journal-title":"Hypertension"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0600571"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.81.2.482"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.61.319"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(91)90038-2"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2002.019166","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2002.019166","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/jphysiol.2002.019166","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2002.019166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T16:55:35Z","timestamp":1693846535000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2002.019166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,7]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,7]]}},"alternative-id":["10.1113\/jphysiol.2002.019166"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2002.019166","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,7]]}}}