{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T09:14:23Z","timestamp":1726478063535},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3931,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Vasomotor function of the vascular endothelium was examined in human subcutaneous arteries excised from 8 hypercholesterolaemic and 7 normolipidaemic subjects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Left gluteal skin biopsies were performed under local anaesthesia. Subcutaneous arteries were isolated and two vessels from each subject mounted in separate myographs. A 20 ml fasting blood sample was taken at the time of the biopsy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hypercholesterolaemic subjects had either never been treated with lipid lowering therapy or therapy had been stopped at least two weeks before the study (<jats:italic>n<\/jats:italic>=2). At the time of the study total plasma cholesterol levels (control: 4.6\u00b10.3 vs hypercholesterolaemic: 8.3\u00b10.6 mmol l<jats:sup>\u22121<\/jats:sup>: <jats:italic>P<\/jats:italic>&lt;0.01) were significantly elevated in hypercholesterolaemic subjects when compared with controls.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Full concentration\u2010response curves to the vasoconstrictor noradrenaline and the vasodilators acetylcholine and substance P were constructed. A single point concentration\u2010response to sodium nitroprusside (10 \u03bc<jats:sc>M<\/jats:sc>) was also obtained. Dilator responses were obtained in vessels pre\u2010constricted with a submaximal concentration of noradrenaline. Vessels were then incubated for 30 min with either <jats:sc>L<\/jats:sc>\u2010 or <jats:sc>D<\/jats:sc>\u2010arginine (10 \u03bc<jats:sc>M<\/jats:sc>) and the concentration\u2010response curves to the three dilator agonists repeated in the presence of the amino acid.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Maximum relaxation responses to acetylcholine (control vs hypercholesterolaemic: 83.3\u00b16.1% vs 47.4\u00b113.5%; <jats:italic>P<\/jats:italic>&lt;0.05), but not to substance P or sodium nitroprusside, were dampened in the hypercholesterolaemic group when compared with controls.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Neither incubation with <jats:sc>L<\/jats:sc>\u2010arginine nor <jats:sc>D<\/jats:sc>\u2010arginine had any effect on maximum relaxation responses to acetylcholine in either the control group (pre <jats:sc>L<\/jats:sc>\u2010arginine vs plus <jats:sc>L<\/jats:sc>\u2010arginine: 83.3\u00b16.1 vs 82.3\u00b15.5%, pre <jats:sc>D<\/jats:sc>\u2010arginine vs plus <jats:sc>D<\/jats:sc>\u2010arginine: 98.9\u00b11.2 vs 98.2\u00b11.1%) or the hypercholesterolaemic group (pre <jats:sc>L<\/jats:sc>\u2010arginine vs plus <jats:sc>L<\/jats:sc>\u2010arginine: 47.4\u00b113.5 vs 55.3\u00b114.3%, pre <jats:sc>D<\/jats:sc>\u2010arginine vs plus D\u2010argenine: 43.3\u00b113.6 vs 65.4\u00b112.3%).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>When results from the two study groups were pooled, the strongest predictor of maximum relaxation obtained to acetylcholine was apolipoprotein A<jats:sub>1<\/jats:sub> (<jats:italic>r<\/jats:italic>=0.67; <jats:italic>P<\/jats:italic>=0.001).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, relaxation responses mediated by the endothelium\u2010dependent agonist acetylcholine, but not by substance P, are impaired in hypercholesterolaemic patients. <jats:sc>L<\/jats:sc>\u2010Arginine did not improve the impaired relaxation responses to acetylcholine. We suggest that impaired endothelium\u2010dependent relaxation is specific to acetylcholine and not to an abnormal <jats:sc>L<\/jats:sc>\u2010arginine\u2010nitric oxide pathway in subcutaneous arteries excised from this study group.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701800","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:29:55Z","timestamp":1106940595000},"page":"222-228","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Responses to endothelium\u2010dependent agonists in subcutaneous arteries excised from hypercholesterolaemic men"],"prefix":"10.1111","volume":"124","author":[{"given":"Tamara V","family":"Lewis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bridget A","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony M","family":"Dart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaye P F","family":"Chin\u2010Dusting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112779"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb13358.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90628-9"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1986.03380200073024"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb13111.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115549"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1994.tb02442.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199607000-00023"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)92621-L"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114688"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115987"},{"key":"e_1_2_6_13_1","first-page":"455","article-title":"Atherosclerotic human coronary vessels preserve a dilator response to substance P in vivo","volume":"61","author":"Crossman D.C.","year":"1989","journal-title":"Br. 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