Augmentation of coronary responsiveness to serotonin at the site of X-ray-induced intimal thickening in miniature pigs
Mitsuoka, Wataru; Egashira, Shogo; Tagawa, Hirofumi; Kuga, Takeshi; Hayashi, Yasuo; Yamada, Akira; Tomoike, Hitonobu; Nakamura, Motoomi; Takeshita, Akira; Mitsuoka Wataru; <sup>a</sup>Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan; Egashira Shogo; <sup>a</sup>Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan; Tagawa Hirofumi; <sup>a</sup>Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan; Kuga Takeshi; <sup>a</sup>Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan; Hayashi Yasuo; <sup>a</sup>Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan; Yamada Akira; <sup>a</sup>Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan; Tomoike Hitonobu; <sup>b</sup>First Division of Internal Medicine, Faculty of Medicine, Yamagata University, Yamagata, Japan; Nakamura Motoomi; <sup>c</sup>Nakamura Gakuen, Graduate School of Nutritional Science, Fukuoka, Japan; Takeshita Akira; <sup>a</sup>Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan
Журнал:
Cardiovascular Research
Дата:
1995
Аннотация:
AbstractObjective: X-irradiation is known to enhance atherosclerotic change. We tested whether coronary vasoconstrictor responses are augmented at the sites of X-ray-induced intimal thickening in Göttingen miniature pigs. Methods: In 17 pigs, a major branch of the left coronary artery was denuded with a balloon catheter. In 10 pigs, the denuded portion of the left coronary artery was selectively irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group 1). The remaining 7 pigs were not irradiated (group 2). The effects of intracoronary administration of serotonin, histamine and phenylephrine on the coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After the angiographical study at 5M, the vessels were isolated and isometric tension was measured in an organ chamber. Results: The percent reduction in coronary diameter evoked with 10 μg · kg<sup>−1</sup> of serotonin increased from 39(s.e.m. 4)% before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 (P < 0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was frequently accompanied by ischemic ECG changes. Histamine (10 μg · kg<sup>−1</sup>)-induced vasoconstriction was also augmented but to a smaller degree [47(6)% at 3M vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group 2 [52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro studies, endothelium-dependent relaxation to serotonin was impaired at the denuded site with (group 1) and without (group 2) X-irradiation to a similar extent. Isometric tension of medial smooth muscle developed by serotonin was significantly greater at the denuded site with X-irradiation (group 1) than the control site and the denuded site without X-irradiation (group 2) (P < 0.05). Intimal thickening was significantly greater at the denuded sites with X-irradiation [group 1, 238(45) μm] than at the denuded sites without X-irradiation [group 2, 58(5) μm] (P < 0.05). Conclusions: These results indicate that X-irradiation augments the coronary vasoconstrictor responses to autacoids, predominantly to serotonin, and that this augmentation is accompanied by enhanced intimal thickening. Serotonin-induced hypercontraction after X-irradiation resulted mainly from the hyperreactivity of medial smooth muscle.
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