Murohara T, Yasue H, Ohgushi M, Sakaino N, Jougasaki M
Division of Cardiology, Kumamoto University Medical School, Japan.
Cardiovasc Res. 1991 Dec;25(12):1002-9. doi: 10.1093/cvr/25.12.1002.
The aim was to investigate the relationship between vascular aging and endothelial regulation of the vascular tone by various agonists in isolated pig coronary arteries. EXPERIMENTAL MATERIALS AND DESIGN: Coronary artery rings from young (4-6 month old) and aged (3-4 years old) Yorkshire pigs were studied under isometric tension by organ chamber experiments. Cumulative concentration-response curves were obtained for vasorelaxing agents including noradrenaline (with beta blocker), substance P, bradykinin, and glyceryl trinitrate in rings precontracted with prostaglandin F2 alpha (PGF2 alpha). The degree of atherosclerosis of the coronary arteries was examined by light microscopy after the pharmacological experiments.
In the presence of propranolol (3 x 10(-6)M), noradrenaline (10(-8)-10(-5)M) caused endothelium dependent relaxation. The maximum relaxation was significantly greater in the young [45.4(SEM 2.5)% of the magnitude of precontraction induced by PGF2 alpha] than in the aged group [26.9(3.0)%] (p less than 0.001). However, magnitudes of relaxation to substance P, bradykinin, and glyceryl trinitrate were not significantly different between the young and the aged groups. The alpha 2 antagonist yohimbine (3 x 10(-6)M) inhibited the endothelium dependent relaxation to noradrenaline, but the alpha 1 antagonist prazosin (10(-6)M) failed to inhibit the response. Gossypol (3 x 10(-5)M) and methylene blue (10(-5)M), both inhibitors of endothelium dependent relaxation, abolished alpha 2 adrenoceptor mediated relaxation, but a cyclo-oxygenase inhibitor indomethacin (10(-5)M) did not affect the response. Histologically almost all young pig coronary arteries were free of atherosclerotic changes, whereas aged arteries had fatty streaks with slightly narrowed lumen in 22 of 38 rings (58%). The remaining aged pig coronary rings were free from atherosclerosis. Comparison of the endothelium dependent relaxation to noradrenaline between the rings with fatty streaks and those without lesions in the aged pigs suggested that the attenuated response was due both to vascular aging and to fatty streak development.
The endothelium dependent relaxation to noradrenaline via the alpha 2 adrenoceptor was attenuated by vascular aging and also by fatty streak formation in isolated pig coronary arteries. Thus vascular aging may affect the sympathetic regulation of the coronary arterial tone by the attenuation of endothelium dependent relaxation to catecholamines via alpha 2 adrenoceptors.
旨在研究离体猪冠状动脉中血管衰老与各种激动剂对血管张力的内皮调节之间的关系。
通过器官浴槽实验，在等长张力条件下研究来自年轻（4 - 6月龄）和老年（3 - 4岁）约克夏猪的冠状动脉环。在用前列腺素F2α（PGF2α）预收缩的血管环中，获得了包括去甲肾上腺素（加β受体阻滞剂）、P物质、缓激肽和硝酸甘油在内的血管舒张剂的累积浓度 - 反应曲线。药理实验后，通过光学显微镜检查冠状动脉的动脉粥样硬化程度。
在普萘洛尔（3×10⁻⁶M）存在的情况下，去甲肾上腺素（10⁻⁸ - 10⁻⁵M）引起内皮依赖性舒张。年轻组的最大舒张幅度[PGF2α诱导的预收缩幅度的45.4（标准误2.5）%]显著大于老年组[26.9（3.0）%]（p < 0.001）。然而，年轻组和老年组对P物质、缓激肽和硝酸甘油的舒张幅度没有显著差异。α₂拮抗剂育亨宾（3×10⁻⁶M）抑制了对去甲肾上腺素的内皮依赖性舒张，但α₁拮抗剂哌唑嗪（10⁻⁶M）未能抑制该反应。内皮依赖性舒张的两种抑制剂棉酚（3×10⁻⁵M）和亚甲蓝（10⁻⁵M）消除了α₂肾上腺素能受体介导的舒张，但环氧化酶抑制剂吲哚美辛（10⁻⁵M）不影响该反应。组织学上，几乎所有年轻猪的冠状动脉都没有动脉粥样硬化改变，而老年猪的动脉在38个血管环中有22个（58%）出现了脂肪条纹，管腔略有狭窄。其余老年猪的冠状动脉环没有动脉粥样硬化。对老年猪中有脂肪条纹的血管环和无病变的血管环之间对去甲肾上腺素的内皮依赖性舒张进行比较表明，反应减弱是由于血管衰老和脂肪条纹形成共同导致的。
在离体猪冠状动脉中，通过α₂肾上腺素能受体对去甲肾上腺素的内皮依赖性舒张因血管衰老和脂肪条纹形成而减弱。因此，血管衰老可能通过减弱经由α₂肾上腺素能受体对儿茶酚胺的内皮依赖性舒张来影响冠状动脉张力的交感神经调节。
