Matsuoka N, Arakawa H, Kodama H, Yamaguchi I
Basic Research Group, Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
J Pharmacol Exp Ther. 1998 Jan;284(1):125-35.
Stress is known clinically and experimentally to contribute to the development or exacerbation of cardiovascular dysfunction. In an attempt to construct an animal model of stress-induced cardiovascular dysfunction and to understand its mechanisms, the effects of cold-immobilization stress and its cardiovascular consequences were investigated in cardiomyopathic Syrian hamsters (BIO 14.6) and age-matched healthy control hamsters. Repeated exposure (5 days) to cold-immobilization in the supine position induced no detectable ill effects in the healthy control hamsters but had a lethal effect in the cardiomyopathic hamsters: more than half of the animals died suddenly during or after the stress sessions. Autopsy study of these animals showed significant increases in the weights of the heart, adrenal, liver and kidney and in the serum levels of alkaline phosphatase, urea nitrogen, creatinine and glucose in the cardiomyopathic hamsters subjected to the stress. Propranolol (0.1-10 mg/kg i.p.) administered just before each cold-immobilization for 5 consecutive days dose-dependently and significantly prevented the lethal effects of the stress. Furthermore, it was demonstrated that the drug significantly reduced the increase in the weights of the heart, adrenal, liver and kidney observed in the stressed cardiomyopathic hamsters, whereas phentolamine (0.1-10 mg/kg) and atropine (0.1-10 mg/kg) did not prevent the stress-induced sudden death. The series of acute experiments using single exposure of this stress revealed that the stress evoked severe arrhythmia in some of the cardiomyopathic hamsters and increased the levels of circulating catecholamines in both healthy and cardiomyopathic hamsters. These results taken together suggest that stress accelerates the cardiovascular dysfunction in cardiomyopathic hamsters and provide the first evidence that excitation of the sympathetic nerves, in which beta-adrenoceptors appear to be involved, but not the parasympathetic nerves, has an important role in the etiology of stress-induced cardiac sudden death of cardiomyopathic hamsters.
临床上和实验中均已证实，应激会促使心血管功能障碍的发生或加重。为构建应激诱导的心血管功能障碍动物模型并了解其机制，我们研究了冷束缚应激对心肌病叙利亚仓鼠（BIO 14.6）和年龄匹配的健康对照仓鼠的影响及其心血管后果。在仰卧位重复暴露（5天）于冷束缚对健康对照仓鼠未产生可检测到的不良影响，但对心肌病仓鼠具有致死作用：超过一半的动物在应激期间或之后突然死亡。对这些动物的尸检研究表明，遭受应激的心肌病仓鼠的心脏、肾上腺、肝脏和肾脏重量显著增加，血清碱性磷酸酶、尿素氮、肌酐和葡萄糖水平也显著升高。在每次冷束缚前连续5天腹腔注射普萘洛尔（0.1 - 10 mg/kg）剂量依赖性且显著地预防了应激的致死作用。此外，已证明该药物显著降低了应激的心肌病仓鼠中观察到的心脏、肾上腺、肝脏和肾脏重量的增加，而酚妥拉明（0.1 - 10 mg/kg）和阿托品（0.1 - 10 mg/kg）不能预防应激诱导的猝死。使用单次暴露这种应激的一系列急性实验表明，应激在一些心肌病仓鼠中诱发了严重心律失常，并增加了健康和心肌病仓鼠的循环儿茶酚胺水平。综合这些结果表明，应激加速了心肌病仓鼠的心血管功能障碍，并首次提供证据表明交感神经兴奋（其中β - 肾上腺素能受体似乎参与其中）而非副交感神经兴奋在心肌病仓鼠应激诱导的心脏猝死病因中起重要作用。
