Wines P A, Schmitz J M, Pfister S L, Clubb F J, Buja L M, Willerson J T, Campbell W B
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Arteriosclerosis. 1989 Mar-Apr;9(2):195-202. doi: 10.1161/01.atv.9.2.195.
Watanabe heritable hyperlipidemic (WHHL) rabbits have elevated concentrations of plasma cholesterol and develop progressive atherosclerosis. The present investigation was undertaken to evaluate the vascular responses to vasoactive compounds of aorta from WHHL rabbits and normal New Zealand White (NZW) rabbits at 1 and 6 months of age. Rings of distal thoracic aorta were suspended under isometric tension in oxygenated Krebs buffer. Developed tension was measured in response to graded concentrations of agonists. Maximal responses to KCl (40 mM) were the same in aortas from the 1-month-old and 6-month-old WHHL and NZW rabbits. Aortas from 1-month-old animals were more sensitive to serotonin than aortas from 6-month-old animals. Aortas from WHHL rabbits exhibited an increased maximal response to serotonin when compared with NZW controls. In contrast, the constrictor responses to norepinephrine were reduced in WHHL rabbits compared with NZW rabbits at both age groups. Methacholine decreased tension development in serotonin-contracted vessels. This relaxation was greatest in aortas from NZW rabbits. In 1-month-old NZW rabbits fed a high cholesterol diet, the constrictor responses to serotonin and the relaxation responses to methacholine did not differ from NZW rabbits ingesting a normal diet. However, the responses to norepinephrine were markedly attenuated in the hypercholesterolemic NZW rabbits. Microscopic evaluation of the aortas revealed occasional adherent leukocytes and irregularities in the vascular endothelium in 1-month-old WHHL animals. These changes were greater in aortas from 6-month-old WHHL animals, with more adherent leukocytes, adherent platelets, and severe irregularities in the endothelial surface.(ABSTRACT TRUNCATED AT 250 WORDS)
渡边遗传性高脂血症（WHHL）兔血浆胆固醇浓度升高，并会发展为进行性动脉粥样硬化。本研究旨在评估1月龄和6月龄的WHHL兔及正常新西兰白兔（NZW）的主动脉对血管活性化合物的血管反应。将胸主动脉远端环段置于含氧的 Krebs 缓冲液中，以等长张力悬挂。测量对不同浓度激动剂的张力变化。1月龄和6月龄的WHHL兔及NZW兔的主动脉对氯化钾（40 mM）的最大反应相同。1月龄动物的主动脉比6月龄动物的主动脉对血清素更敏感。与NZW对照相比，WHHL兔的主动脉对血清素的最大反应增加。相反，在两个年龄组中，与NZW兔相比，WHHL兔对去甲肾上腺素的收缩反应降低。乙酰甲胆碱可降低血清素收缩血管的张力。这种舒张作用在NZW兔的主动脉中最为明显。在喂食高胆固醇饮食的1月龄NZW兔中，对血清素 的收缩反应和对乙酰甲胆碱的舒张反应与喂食正常饮食的NZW兔没有差异。然而，高胆固醇血症的NZW兔对去甲肾上腺素的反应明显减弱。对主动脉的显微镜评估显示，1月龄WHHL动物的主动脉偶尔有黏附的白细胞和血管内皮不规则。这些变化在6月龄WHHL动物的主动脉中更明显，有更多黏附的白细胞、黏附的血小板，且内皮表面有严重不规则。（摘要截短于250字）
